Exploration of Drug Science

Table 1. Family of CCK bioactive peptide hormones present in humans

CCK forms	Affinity CCK₁r	Affinity CCK₂r	Release location	CCK C-terminal fragments (sequence of aa residues)
CCK-4	No	Yes	Brain	Trp-Met-Asp-Phe-NH₂
CCK-8NS	No	Yes	Digestive tract	Asp-Tyr-Met-Gly-Trp-Met-Asp-Phe-NH₂
CCK-8S	Yes	Yes	Brain	Asp-Tyr(SO₃H)-Met-Gly-Trp-Met-Asp-Phe-NH₂
CCK-12S	Yes	Yes	Digestive tract	Ile-Ser-Asp-Arg-Asp-Tyr(SO₃H)-Met-Gly-Trp-Met-Asp-Phe-NH₂
CCK-22S	Yes	Yes	Digestive tract	Asn-Leu-Gln-Asn-Leu-Asp-Pro-Ser-His-Arg-Ile-Ser-Asp-Arg-Asp-Tyr(SO₃H)-Met-Gly-Trp-Met-Asp-Phe-NH₂
CCK-33S	Yes	Yes	Digestive tract	Lys-Ala-Pro-Ser-Gly-Arg-Met-Ser-Ile-Val-Lys-Asn-Leu-Gln-Asn-Leu-Asp-Pro-Ser-His-Arg-Ile-Ser-Asp-Arg-Asp-Tyr(SO₃H)-Met-Gly-Trp-Met-Asp-Phe-NH₂
CCK-58S	Yes	Yes	Digestive tract	Val-Ser-Gln-Arg-Thr-Asp-Gly-Glu-Ser-Arg-Ala-His-Leu-Gly-Ala-Leu-Leu-Ala-Arg-Tyr-Ile-Gln-Gln-Ala-Arg-Lys-Ala-Pro-Ser-Gly-Arg-Met-Ser-Ile-Val-Lys-Asn-Leu-Gln-Asn-Leu-Asp-Pro-Ser-His-Arg-Ile-Ser-Asp-Arg-Asp-Tyr(SO₃H)-Met-Gly-Trp-Met-Asp-Phe-NH₂

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CCK: cholecystokinin; CCK-4: CCK tetrapeptide; CCK-8NS: non-sulfated CCK octapeptide; CCK-8S: sulfated CCK octapeptide; CCK-12S: sulfated 12-aa CCK; CCK-22S: sulfated 22-aa CCK; CCK-33S: sulfated 33-aa CCK; CCK-58S: sulfated 58-aa CCK

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Author contributions

SJB: Conceptualization, Investigation, Methodology, Validation, Writing—original draft, Writing—review & editing.

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Not applicable.

Conflicts of interest

Santiago J. Ballaz, who is the Guest Editor of Exploration of Drug Science, had no involvement in the decision-making or the review process of this manuscript.

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References

Rehfeld JF. Cholecystokinin - portrayal of an unfolding peptide messenger system. Peptides. 2025;186:171369. [DOI] [PubMed]

Beinfeld MC. Chapter 99 - CCK/Gastrin. In: Kastin AJ, edtior. Handbook of Biologically Active Peptides. Burlington: Academic Press; 2006. pp. 715–20. [DOI]

Asim M, Wang H, Waris A, Qianqian G, Chen X. Cholecystokinin neurotransmission in the central nervous system: Insights into its role in health and disease. Biofactors. 2024;50:1060–75. [DOI] [PubMed] [PMC]

Innis RB, Snyder SH. Distinct cholecystokinin receptors in brain and pancreas. Proc Natl Acad Sci U S A. 1980;77:6917–21. [DOI] [PubMed] [PMC]

Jensen RT, Qian JM, Lin JT, Mantey SA, Pisegna JR, Wank SA. Distinguishing multiple CCK receptor subtypes. Studies with guinea pig chief cells and transfected human CCK receptors. Ann N Y Acad Sci. 1994;713:88–106. [DOI] [PubMed] [PMC]

Gibbs J, Smith GP. Chapter 11 - Gut Peptides and Feeding Behavior: The Model of Cholecystokinin. In: Ritter RC, Ritter S, Barnes CD, editors. Feeding Behavior Neural and Humoral Controls. Academic Press; 1986. pp. 329–52. [DOI]

Wiesenfeld-Hallin Z, Xu XJ. The role of cholecystokinin in nociception, neuropathic pain and opiate tolerance. Regul Pept. 1996;65:23–8. [DOI] [PubMed]

Benedetti F, Amanzio M, Casadio C, Oliaro A, Maggi G. Blockade of nocebo hyperalgesia by the cholecystokinin antagonist proglumide. Pain. 1997;71:135–40. [DOI] [PubMed]

Hebb ALO, Poulin J, Roach SP, Zacharko RM, Drolet G. Cholecystokinin and endogenous opioid peptides: interactive influence on pain, cognition, and emotion. Prog Neuropsychopharmacol Biol Psychiatry. 2005;29:1225–38. [DOI] [PubMed]

10.

Moran TH, Schwartz GJ. Neurobiology of cholecystokinin. Crit Rev Neurobiol. 1994;9:1–28. [PubMed]

11.

Noble F, Roques BP. Cholecystokinin Peptides in Brain Function. In: Lajtha A, Lim R, editors. Handbook of Neurochemistry and Molecular Neurobiology. Boston: Springer; 2006. pp. 545–71. [DOI]

12.

Lau SH, Young CH, Zheng Y, Chen X. The potential role of the cholecystokinin system in declarative memory. Neurochem Int. 2023;162:105440. [DOI] [PubMed]

13.

Bourin M, Malinge M, Vasar E, Bradwejn J. Two faces of cholecystokinin: anxiety and schizophrenia. Fundam Clin Pharmacol. 1996;10:116–26. [DOI] [PubMed]

14.

Ballaz SJ, Bourin M. Cholecystokinin-Mediated Neuromodulation of Anxiety and Schizophrenia: A “Dimmer-Switch” Hypothesis. Curr Neuropharmacol. 2021;19:925–38. [DOI] [PubMed] [PMC]

15.

Drozd MM, Capovilla M, Previderé C, Grossi M, Askenazy F, Bardoni B, et al. A Pilot Study on Early-Onset Schizophrenia Reveals the Implication of Wnt, Cadherin and Cholecystokinin Receptor Signaling in Its Pathophysiology. Front Genet. 2021;12:792218. [DOI] [PubMed] [PMC]

16.

Barde S, Aguila J, Zhong W, Solarz A, Mei I, Prud'homme J, et al. Substance P, NPY, CCK and their receptors in five brain regions in major depressive disorder with transcriptomic analysis of locus coeruleus neurons. Eur Neuropsychopharmacol. 2024;78:54–63. [DOI] [PubMed]

17.

Jahangard L, Solgy R, Salehi I, Taheri SK, Holsboer-Trachsler E, Haghighi M, et al. Cholecystokinin (CCK) level is higher among first time suicide attempters than healthy controls, but is not associated with higher depression scores. Psychiatry Res. 2018;266:40–6. [DOI] [PubMed]

18.

Crespi F, Corsi M, Reggiani A, Ratti E, Gaviraghi G. Involvement of cholecystokinin within craving for cocaine: role of cholecystokinin receptor ligands. Expert Opin Investig Drugs. 2000;9:2249–58. [DOI] [PubMed]

19.

Ma Y, Giardino WJ. Neural circuit mechanisms of the cholecystokinin (CCK) neuropeptide system in addiction. Addict Neurosci. 2022;3:100024. [DOI] [PubMed] [PMC]

20.

Wang J, Zhang M, Sun Y, Su X, Hui R, Zhang L, et al. The modulation of cholecystokinin receptor 1 in the NAc core input from VTA on METH-induced CPP acquisition. Life Sci. 2025;361:123290. [DOI] [PubMed]

21.

Daugé V, Léna I. CCK in anxiety and cognitive processes. Neurosci Biobehav Rev. 1998;22:815–25. [DOI] [PubMed]

22.

Bradwejn J, Koszycki D. Chapter 22 - Cholecystokinin and panic disorder. In: Feinle-Bisset C, Rehfeld JF, editors. Cholecystokinin. Academic Press; 2025. pp. 505–21. [DOI]

23.

Adams JB, Pyke RE, Costa J, Cutler NR, Schweizer E, Wilcox CS, et al. A double-blind, placebo-controlled study of a CCK-B receptor antagonist, CI-988, in patients with generalized anxiety disorder. J Clin Psychopharmacol. 1995;15:428–34. [DOI] [PubMed]

24.

Kramer MS, Cutler NR, Ballenger JC, Patterson WM, Mendels J, Chenault A, et al. A placebo-controlled trial of L-365,260, a CCK_B antagonist, in panic disorder. Biol Psychiatry. 1995;37:462–6. [DOI] [PubMed]

25.

Pande AC, Greiner M, Adams JB, Lydiard RB, Pierce MW. Placebo-controlled trial of the CCK-B antagonist, CI-988, in panic disorder. Biol Psychiatry. 1999;46:860–2. [DOI] [PubMed]

26.

McCleane GJ. A randomised, double blind, placebo controlled crossover study of the cholecystokinin 2 antagonist L-365,260 as an adjunct to strong opioids in chronic human neuropathic pain. Neurosci Lett. 2003;338:151–4. [DOI] [PubMed]

27.

Abelson JL. Cholecystokinin in psychiatric research: a time for cautious excitement. J Psychiatr Res. 1995;29:389–96. [DOI] [PubMed]

28.

Rotzinger S, Vaccarino FJ. Cholecystokinin receptor subtypes: role in the modulation of anxiety-related and reward-related behaviours in animal models. J Psychiatry Neurosci. 2003;28:171–81. [PubMed] [PMC]

29.

Li H, Ohta H, Izumi H, Matsuda Y, Seki M, Toda T, et al. Behavioral and cortical EEG evaluations confirm the roles of both CCK_A and CCK_B receptors in mouse CCK-induced anxiety. Behav Brain Res. 2013;237:325–32. [DOI] [PubMed]

30.

Männistö PT, Lang A, Harro J, Peuranen E, Bradwejn J, Vasar E. Opposite effects mediated by CCK_A and CCK_B receptors in behavioural and hormonal studies in rats. Naunyn Schmiedebergs Arch Pharmacol. 1994;349:478–84. [DOI] [PubMed]

31.

Smadja C, Maldonado R, Turcaud S, Fournie-Zaluski MC, Roques BP. Opposite role of CCK_A and CCK_B receptors in the modulation of endogenous enkephalin antidepressant-like effects. Psychopharmacology (Berl). 1995;120:400–8. [DOI] [PubMed]

32.

Crawley JN. Subtype-selective cholecystokinin receptor antagonists block cholecystokinin modulation of dopamine-mediated behaviors in the rat mesolimbic pathway. J Neurosci. 1992;12:3380–91. [DOI] [PubMed] [PMC]

33.

Hökfelt T, Rehfeld JF, Skirboll L, Ivemark B, Goldstein M, Markey K. Evidence for coexistence of dopamine and CCK in meso-limbic neurones. Nature. 1980;285:476–8. [DOI] [PubMed]

34.

Marshall FH, Barnes S, Hughes J, Woodruff GN, Hunter JC. Cholecystokinin modulates the release of dopamine from the anterior and posterior nucleus accumbens by two different mechanisms. J Neurochem. 1991;56:917–22. [DOI] [PubMed]

35.

Balleine B, Dickinson A. Role of cholecystokinin in the motivational control of instrumental action in rats. Behav Neurosci. 1994;108:590–605. [DOI] [PubMed]

36.

Ladurelle N, Keller G, Blommaert A, Roques BP, Daugé V. The CCK-B agonist, BC264, increases dopamine in the nucleus accumbens and facilitates motivation and attention after intraperitoneal injection in rats. Eur J Neurosci. 1997;9:1804–14. [DOI] [PubMed]

37.

Higgins GA, Nguyen P, Sellers EM. Morphine place conditioning is differentially affected by CCK_A and CCK_B receptor antagonists. Brain Res. 1992;572:208–15. [DOI] [PubMed]

38.

Noble F, Roques BP. The role of CCK2 receptors in the homeostasis of the opioid system. Drugs Today (Barc). 2003;39:897–908. [DOI] [PubMed]

39.

Pommier B, Beslot F, Simon A, Pophillat M, Matsui T, Dauge V, et al. Deletion of CCK₂ receptor in mice results in an upregulation of the endogenous opioid system. J Neurosci. 2002;22:2005–11. [DOI] [PubMed] [PMC]

40.

Manno FAM, An Z, Su J, Liu J, He J, Wu EX, et al. Cholecystokinin receptor antagonist challenge elicits brain-wide functional connectome modulation with micronetwork hippocampal decreased calcium transients. Cereb Cortex. 2023;33:5863–74. [DOI] [PubMed]

41.

Sebret A, Léna I, Crété D, Matsui T, Roques BP, Daugé V. Rat hippocampal neurons are critically involved in physiological improvement of memory processes induced by cholecystokinin-B receptor stimulation. J Neurosci. 1999;19:7230–7. [DOI] [PubMed] [PMC]

42.

Reisi P, Ghaedamini AR, Golbidi M, Shabrang M, Arabpoor Z, Rashidi B. Effect of cholecystokinin on learning and memory, neuronal proliferation and apoptosis in the rat hippocampus. Adv Biomed Res. 2015;4:227. [DOI] [PubMed] [PMC]

43.

Plagman A, Hoscheidt S, McLimans KE, Klinedinst B, Pappas C, Anantharam V, et al. Cholecystokinin and Alzheimer’s disease: a biomarker of metabolic function, neural integrity, and cognitive performance. Neurobiol Aging. 2019;76:201–7. [DOI] [PubMed] [PMC]

44.

Nguyen R, Sivakumaran S, Lambe EK, Kim JC. Ventral hippocampal cholecystokinin interneurons gate contextual reward memory. iScience. 2024;27:108824. [DOI] [PubMed] [PMC]

45.

Feng T, Alicea C, Pham V, Kirk A, Pieraut S. Experience-Dependent Inhibitory Plasticity Is Mediated by CCK+ Basket Cells in the Developing Dentate Gyrus. J Neurosci. 2021;41:4607–19. [DOI] [PubMed] [PMC]

46.

Balschun D, Reymann KG. Cholecystokinin (CCK-8S) prolongs ‘unsaturated’ θ-pulse induced long-term potentiation in rat hippocampal CA1 in vitro. Neuropeptides. 1994;26:421–7. [DOI] [PubMed]

47.

Chen X, Li X, Wong YT, Zheng X, Wang H, Peng Y, et al. Cholecystokinin release triggered by NMDA receptors produces LTP and sound-sound associative memory. Proc Natl Acad Sci U S A. 2019;116:6397–406. [DOI] [PubMed] [PMC]

48.

Asim M, Wang H, Chen X. Shedding light on cholecystokinin’s role in hippocampal neuroplasticity and memory formation. Neurosci Biobehav Rev. 2024;159:105615. [DOI] [PubMed]

49.

Handelmann GE, Beinfeld MC, OʼDonohue TL, Nelson JB, Brenneman DE. Extra-hippocampal projections of CCK neurons of the hippocampus and subiculum. Peptides. 1983;4:331–4. [DOI] [PubMed]

50.

Crosby KM, Murphy-Royal C, Wilson SA, Gordon GR, Bains JS, Pittman QJ. Cholecystokinin Switches the Plasticity of GABA Synapses in the Dorsomedial Hypothalamus via Astrocytic ATP Release. J Neurosci. 2018;38:8515–25. [DOI] [PubMed] [PMC]

51.

Guerrero DKR, Balueva K, Barayeu U, Baracskay P, Gridchyn I, Nardin M, et al. Hippocampal cholecystokinin-expressing interneurons regulate temporal coding and contextual learning. Neuron. 2024;112:2045–61.e10. [DOI] [PubMed]

52.

Ballaz SJ, Bourin M, Akil H, Watson SJ. Blockade of the cholecystokinin CCK-2 receptor prevents the normalization of anxiety levels in the rat. Prog Neuropsychopharmacol Biol Psychiatry. 2020;96:109761. [DOI] [PubMed] [PMC]

53.

Li H, Feng J, Chen M, Xin M, Chen X, Liu W, et al. Cholecystokinin facilitates motor skill learning by modulating neuroplasticity in the motor cortex. Elife. 2024;13:e83897. [DOI] [PubMed] [PMC]

54.

Cui H, Li Z, Sun H, Zhao W, Ma H, Hao L, et al. The neuroprotective effects of cholecystokinin in the brain: antioxidant, anti-inflammatory, cognition, and synaptic plasticity. Rev Neurosci. 2025;36:339–50. [DOI] [PubMed]

55.

Guillaume C, Sáez M, Parnet P, Reig R, Paillé V. Cholecystokinin Modulates Corticostriatal Transmission and Plasticity in Rodents. eNeuro. 2025;12:ENEURO.0251–24.2025. [DOI] [PubMed] [PMC]

56.

Huang F, Baset A, Bello ST, Chen X, He J. Cholecystokinin facilitates the formation of long-term heterosynaptic plasticity in the distal subiculum. Commun Biol. 2025;8:153. [DOI] [PubMed] [PMC]

57.

Zwanzger P, Domschke K, Bradwejn J. Neuronal network of panic disorder: the role of the neuropeptide cholecystokinin. Depress Anxiety. 2012;29:762–74. [DOI] [PubMed]

58.

Bradwejn J, Koszycki D, Meterissian G. Cholecystokinin-tetrapeptide induces panic attacks in patients with panic disorder. Can J Psychiatry. 1990;35:83–5. [DOI] [PubMed]

59.

Abelson JL, Nesse RM. Pentagastrin infusions in patients with panic disorder. I. Symptoms and cardiovascular responses. Biol Psychiatry. 1994;36:73–83. [DOI] [PubMed]

60.

Schunck T, Erb G, Mathis A, Gilles C, Namer IJ, Hode Y, et al. Functional magnetic resonance imaging characterization of CCK-4-induced panic attack and subsequent anticipatory anxiety. Neuroimage. 2006;31:1197–208. [DOI] [PubMed]

61.

Eser D, Leicht G, Lutz J, Wenninger S, Kirsch V, Schüle C, et al. Functional neuroanatomy of CCK-4-induced panic attacks in healthy volunteers. Hum Brain Mapp. 2009;30:511–22. [DOI] [PubMed] [PMC]

62.

Pérez de la Mora M, Hernández-Gómez AM, Arizmendi-García Y, Jacobsen KX, Lara-García D, Flores-Gracia C, et al. Role of the amygdaloid cholecystokinin (CCK)/gastrin-2 receptors and terminal networks in the modulation of anxiety in the rat. Effects of CCK-4 and CCK-8S on anxiety-like behaviour and [³H]GABA release. Eur J Neurosci. 2007;26:3614–30. [DOI] [PubMed]

63.

Boca CD, Lutz PE, Merrer JL, Koebel P, Kieffer BL. Cholecystokinin knock-down in the basolateral amygdala has anxiolytic and antidepressant-like effects in mice. Neuroscience. 2012;218:185–95. [DOI] [PubMed] [PMC]

64.

Asim M, Wang H, Waris A, He J. Basolateral amygdala parvalbumin and cholecystokinin-expressing GABAergic neurons modulate depressive and anxiety-like behaviors. Transl Psychiatry. 2024;14:418. [DOI] [PubMed] [PMC]

65.

Fang W, Chen X, He J. Cholecystokinin-expressing interneurons mediated inhibitory transmission and plasticity in basolateral amygdala modulate stress-induced anxiety-like behaviors in mice. Neurobiol Stress. 2024;33:100680. [DOI] [PubMed] [PMC]

66.

Vialou V, Bagot RC, Cahill ME, Ferguson D, Robison AJ, Dietz DM, et al. Prefrontal cortical circuit for depression- and anxiety-related behaviors mediated by cholecystokinin: role of ΔFosB. J Neurosci. 2014;34:3878–87. [DOI] [PubMed] [PMC]

67.

Lydiard RB. The role of GABA in anxiety disorders. J Clin Psychiatry. 2003;64:21–7. [PubMed]

68.

Bergink V, van Megen HJ, Westenberg HGM. Glutamate and anxiety. Eur Neuropsychopharmacol. 2004;14:175–83. [DOI] [PubMed]

69.

Peek AL, Rebbeck T, Puts NA, Watson J, Aguila MR, Leaver AM. Brain GABA and glutamate levels across pain conditions: A systematic literature review and meta-analysis of 1H-MRS studies using the MRS-Q quality assessment tool. Neuroimage. 2020;210:116532. [DOI] [PubMed]

70.

Wang JH, Wang D, Gao Z, Chen N, Lei Z, Cui S, et al. Both Glutamatergic and Gabaergic Neurons are Recruited to be Associative Memory Cells. Biophys J. 2016;110:481A. [DOI]

71.

Yan F, Gao Z, Chen P, Huang L, Wang D, Chen N, et al. Coordinated Plasticity between Barrel Cortical Glutamatergic and GABAergic Neurons during Associative Memory. Neural Plast. 2016;2016:5648390. [DOI] [PubMed] [PMC]

72.

Zhao X, Huang L, Guo R, Liu Y, Zhao S, Guan S, et al. Coordinated Plasticity among Glutamatergic and GABAergic Neurons and Synapses in the Barrel Cortex Is Correlated to Learning Efficiency. Front Cell Neurosci. 2017;11:221. [DOI] [PubMed] [PMC]

73.

Armstrong C, Soltesz I. Basket cell dichotomy in microcircuit function. J Physiol. 2012;590:683–94. [DOI] [PubMed] [PMC]

74.

Dudok B, Klein PM, Hwaun E, Lee BR, Yao Z, Fong O, et al. Alternating sources of perisomatic inhibition during behavior. Neuron. 2021;109:997–1012.e9. [DOI] [PubMed] [PMC]

75.

Goettel M, Fuertig R, Mack SR, Just S, Sharma V, Wunder A, et al. Effect of BI 1358894 on Cholecystokinin-Tetrapeptide (CCK-4)-Induced Anxiety, Panic Symptoms, and Stress Biomarkers: A Phase I Randomized Trial in Healthy Males. CNS Drugs. 2023;37:1099–109. [DOI] [PubMed] [PMC]

76.

Zhang X, Asim M, Fang W, Monir HM, Wang H, Kim K, et al. Cholecystokinin B receptor antagonists for the treatment of depression via blocking long-term potentiation in the basolateral amygdala. Mol Psychiatry. 2023;28:3459–74. [DOI] [PubMed]

77.

Rezayat M, Roohbakhsh A, Zarrindast M, Massoudi R, Djahanguiri B. Cholecystokinin and GABA interaction in the dorsal hippocampus of rats in the elevated plus-maze test of anxiety. Physiol Behav. 2005;84:775–82. [DOI] [PubMed]

78.

Moghaddam AH, Hosseini RS, Roohbakhsh A. Anxiogenic effect of CCK8s in the ventral hippocampus of rats: possible involvement of GABA_A receptors. Pharmacol Rep. 2012;64:45–53. [DOI] [PubMed]

79.

Chung L, Moore SD. Cholecystokinin enhances GABAergic inhibitory transmission in basolateral amygdala. Neuropeptides. 2007;41:453–63. [DOI] [PubMed]

80.

Antonelli T, Tomasini MC, Mazza R, Fuxe K, Gaetani S, Cuomo V, et al. Cannabinoid CB₁ and cholecystokinin CCK₂ receptors modulate, in an opposing way, electrically evoked [³H]GABA efflux from rat cerebral cortex cell cultures: possible relevance for cortical GABA transmission and anxiety. J Pharmacol Exp Ther. 2009;329:708–17. [DOI] [PubMed]

81.

Deng P, Xiao Z, Jha A, Ramonet D, Matsui T, Leitges M, et al. Cholecystokinin facilitates glutamate release by increasing the number of readily releasable vesicles and releasing probability. J Neurosci. 2010;30:5136–48. [DOI] [PubMed] [PMC]

82.

Reich N, Hölscher C. Cholecystokinin (CCK): a neuromodulator with therapeutic potential in Alzheimerʼs and Parkinsonʼs disease. Front Neuroendocrinol. 2024;73:101122. [DOI] [PubMed]

83.

Miller KK, Hoffer A, Svoboda KR, Lupica CR. Cholecystokinin increases GABA release by inhibiting a resting K⁺ conductance in hippocampal interneurons. J Neurosci. 1997;17:4994–5003. [DOI] [PubMed] [PMC]

84.

Whissell PD, Bang JY, Khan I, Xie Y, Parfitt GM, Grenon M, et al. Selective Activation of Cholecystokinin-Expressing GABA (CCK-GABA) Neurons Enhances Memory and Cognition. eNeuro. 2019;6:ENEURO.0360–18.2019. [DOI] [PubMed] [PMC]

85.

Roca-Lapirot O, Fossat P, Ma S, Egron K, Trigilio G, López-González M, et al. Acquisition of analgesic properties by the cholecystokinin (CCK)/CCK₂ receptor system within the amygdala in a persistent inflammatory pain condition. Pain. 2019;160:345–57. [DOI] [PubMed]

86.

Bernard A, Danigo A, Bourthoumieu S, Mroué M, Desmoulière A, Sturtz F, et al. The Cholecystokinin Type 2 Receptor, a Pharmacological Target for Pain Management. Pharmaceuticals (Basel). 2021;14:1185. [DOI] [PubMed] [PMC]

87.

LaVigne JE, Alles SRA. CCK2 receptors in chronic pain. Neurobiol Pain. 2022;11:100092. [DOI] [PubMed] [PMC]

88.

Poulson SJ, Skvortsova A, Paz LV, Cui W, Mandatori A, Burek J, et al. Cholecystokinin input from the anterior cingulate cortex to the lateral periaqueductal gray mediates nocebo pain behavior in mice. BioRxiv [Preprint]. 2025 [cited 2025 Feb 6]. Available from: https://www.biorxiv.org/content/10.1101/2025.02.04.636522v1

89.

Lovick TA. Pro-nociceptive action of cholecystokinin in the periaqueductal grey: a role in neuropathic and anxiety-induced hyperalgesic states. Neurosci Biobehav Rev. 2008;32:852–62. [DOI] [PubMed]

90.

Netto CF, Guimarães FS. Anxiogenic effect of cholecystokinin in the dorsal periaqueductal gray. Neuropsychopharmacology. 2004;29:101–7. [DOI] [PubMed]

91.

Zanoveli JM, Netto CF, Guimarães FS, Zangrossi H Jr. Systemic and intra-dorsal periaqueductal gray injections of cholecystokinin sulfated octapeptide (CCK-8s) induce a panic-like response in rats submitted to the elevated T-maze. Peptides. 2004;25:1935–41. [DOI] [PubMed]

92.

Bertoglio LJ, Zangrossi H Jr. Involvement of dorsolateral periaqueductal gray cholecystokinin-2 receptors in the regulation of a panic-related behavior in rats. Brain Res. 2005;1059:46–51. [DOI] [PubMed]

93.

Vázquez-León P, Campos-Rodríguez C, Gonzalez-Pliego C, Miranda-Páez A. Differential effects of cholecystokinin (CCK-8) microinjection into the ventrolateral and dorsolateral periaqueductal gray on anxiety models in Wistar rats. Horm Behav. 2018;106:105–11. [DOI] [PubMed]

94.

Ströhle A, Holsboer F, Rupprecht R. Increased ACTH concentrations associated with cholecystokinin tetrapeptide-induced panic attacks in patients with panic disorder. Neuropsychopharmacology. 2000;22:251–6. [DOI] [PubMed]

95.

Abelson JL, Young EA. Hypothalamic-pituitary adrenal response to cholecystokinin-B receptor agonism is resistant to cortisol feedback inhibition. Psychoneuroendocrinology. 2003;28:169–80. [DOI] [PubMed]

96.

Demiralay C, Jahn H, Kellner M, Yassouridis A, Wiedemann K. Differential effects to CCK-4-induced panic by dexamethasone and hydrocortisone. World J Biol Psychiatry. 2012;13:526–34. [DOI] [PubMed]

97.

Yamaguchi N, Hosomi E, Hori Y, Ro S, Maezawa K, Ochiai M, et al. The Combination of Cholecystokinin and Stress Amplifies an Inhibition of Appetite, Gastric Emptying, and an Increase in c-Fos Expression in Neurons of the Hypothalamus and the Medulla Oblongata. Neurochem Res. 2020;45:2173–83. [DOI] [PubMed]

98.

Geracioti TD Jr, Ekhator NN, Nicholson WE, Arndt S, Loosen PT, Orth DN. Intra- and inter-individual correlations between cholecystokinin and corticotropin-releasing hormone concentrations in human cerebrospinal fluid. Depress Anxiety. 1999;10:77–80. [DOI] [PubMed]

99.

Burdakov D, Peleg-Raibstein D. The hypothalamus as a primary coordinator of memory updating. Physiol Behav. 2020;223:112988. [DOI] [PubMed]

100.

Wingenfeld K, Wolf OT. HPA axis alterations in mental disorders: impact on memory and its relevance for therapeutic interventions. CNS Neurosci Ther. 2011;17:714–22. [DOI] [PubMed] [PMC]

101.

Juaneda C, Lafon-Dubourg P, Ciofi P, Sarrieau A, Wenger T, Tramu G, et al. CCK mRNA expression in neuroendocrine CRH neurons is increased in rats subjected to an immune challenge. Brain Res. 2001;901:277–80. [DOI] [PubMed]

102.

Wang H, Spiess J, Wong PT, Zhu YZ. Blockade of CRF1 and CCK2 receptors attenuated the elevated anxiety-like behavior induced by immobilization stress. Pharmacol Biochem Behav. 2011;98:362–8. [DOI] [PubMed]

103.

Bhatnagar S, Viau V, Chu A, Soriano L, Meijer OC, Dallman MF. A cholecystokinin-mediated pathway to the paraventricular thalamus is recruited in chronically stressed rats and regulates hypothalamic-pituitary-adrenal function. J Neurosci. 2000;20:5564–73. [DOI] [PubMed] [PMC]

104.

Herman JP, Tasker JG. Paraventricular Hypothalamic Mechanisms of Chronic Stress Adaptation. Front Endocrinol (Lausanne). 2016;7:137. [DOI] [PubMed] [PMC]

105.

Herman JP. Regulation of Hypothalamo-Pituitary-Adrenocortical Responses to Stressors by the Nucleus of the Solitary Tract/Dorsal Vagal Complex. Cell Mol Neurobiol. 2018;38:25–35. [DOI] [PubMed] [PMC]

106.

Corp ES, McQuade J, Moran TH, Smith GP. Characterization of type A and type B CCK receptor binding sites in rat vagus nerve. Brain Res. 1993;623:161–6. [DOI] [PubMed]

107.

Flood JF, Smith GE, Morley JE. Modulation of memory processing by cholecystokinin: dependence on the vagus nerve. Science. 1987;236:832–4. [DOI] [PubMed]

108.

Itoh S, Lal H. Influences of cholecystokinin and analogues on memory processes. Drug Develop Res. 1990;21:257–76. [DOI]

109.

Cao B, Zhang X, Yan N, Chen S, Li Y. Cholecystokinin enhances visceral pain-related affective memory via vagal afferent pathway in rats. Mol Brain. 2012;5:19. [DOI] [PubMed] [PMC]

110.

Hisadome K, Reimann F, Gribble FM, Trapp S. CCK stimulation of GLP-1 neurons involves α₁-adrenoceptor-mediated increase in glutamatergic synaptic inputs. Diabetes. 2011;60:2701–9. [DOI] [PubMed] [PMC]

111.

Day HE, McKnight AT, Poat JA, Hughes J. Evidence that cholecystokinin induces immediate early gene expression in the brainstem, hypothalamus and amygdala of the rat by a CCK_A receptor mechanism. Neuropharmacology. 1994;33:719–27. [DOI] [PubMed]

112.

Su J, Huang F, Tian Y, Tian R, Qianqian G, Bello ST, et al. Entorhinohippocampal cholecystokinin modulates spatial learning by facilitating neuroplasticity of hippocampal CA3-CA1 synapses. Cell Rep. 2023;42:113467. [DOI] [PubMed]

113.

Huang F, Bello ST. Neuropeptide cholecystokinin: a key neuromodulator for hippocampal functions. Neural Regen Res. 2025;20:1991–2. [DOI] [PubMed] [PMC]

114.

Lemaire M, Barnéoud P, Böhme GA, Piot O, Haun F, Roques BP, et al. CCK-A and CCK-B receptors enhance olfactory recognition via distinct neuronal pathways. Learn Mem. 1994;1:153–64. [PubMed]

115.

Nomoto S, Miyake M, Ohta M, Funakoshi A, Miyasaka K. Impaired learning and memory in OLETF rats without cholecystokinin (CCK)-A receptor. Physiol Behav. 1999;66:869–72. [DOI] [PubMed]

116.

Suarez AN, Hsu TM, Liu CM, Noble EE, Cortella AM, Nakamoto EM, et al. Gut vagal sensory signaling regulates hippocampus function through multi-order pathways. Nat Commun. 2018;9:2181. [DOI] [PubMed] [PMC]

117.

Li X, Yu K, Zhang Z, Sun W, Yang Z, Feng J, et al. Cholecystokinin from the entorhinal cortex enables neural plasticity in the auditory cortex. Cell Res. 2014;24:307–30. [DOI] [PubMed] [PMC]

118.

Nguyen R, Venkatesan S, Binko M, Bang JY, Cajanding JD, Briggs C, et al. Cholecystokinin-Expressing Interneurons of the Medial Prefrontal Cortex Mediate Working Memory Retrieval. J Neurosci. 2020;40:2314–31. [DOI] [PubMed] [PMC]

119.

Sun W, Wu H, Peng Y, Zheng X, Li J, Zeng D, et al. Heterosynaptic plasticity of the visuo-auditory projection requires cholecystokinin released from entorhinal cortex afferents. Elife. 2024;13:e83356. [DOI] [PubMed] [PMC]

120.

Bandopadhyay R, de Belleroche J. Regulation of CCK release in cerebral cortex by N-methyl-D-aspartate receptors: sensitivity to APV, MK-801, kynurenate, magnesium and zinc ions. Neuropeptides. 1991;18:159–63. [DOI] [PubMed]

121.

Wong Y, Zheng X, Lau S, Sun KM, Chen X, Li H, et al. Artificial fluorescent sensor reveals pre-synaptic NMDA receptors switch cholecystokinin release and LTP in the hippocampus. J Neurochem. 2024;168:2621–39. [DOI] [PubMed]

122.

Kalueff AV. Neurobiology of memory and anxiety: from genes to behavior. Neural Plast. 2007;2007:78171. [DOI] [PubMed] [PMC]

123.

Eldar S, Bar-Haim Y. Neural plasticity in response to attention training in anxiety. Psychol Med. 2010;40:667–77. [DOI] [PubMed]

124.

Månsson KNT, Salami A, Frick A, Carlbring P, Andersson G, Furmark T, et al. Neuroplasticity in response to cognitive behavior therapy for social anxiety disorder. Transl Psychiatry. 2016;6:e727. [DOI] [PubMed] [PMC]

125.

Melzack R, Coderre TJ, Katz J, Vaccarino AL. Central neuroplasticity and pathological pain. Ann N Y Acad Sci. 2001;933:157–74. [DOI] [PubMed]

126.

Feng H, Su J, Fang W, Chen X, He J. The entorhinal cortex modulates trace fear memory formation and neuroplasticity in the mouse lateral amygdala via cholecystokinin. Elife. 2021;10:e69333. [DOI] [PubMed] [PMC]

127.

Philipp E, Wilckens T, Friess E, Platte P, Pirke KM. Cholecystokinin, gastrin and stress hormone responses in marathon runners. Peptides. 1992;13:125–8. [DOI] [PubMed]

128.

Zhang Z, Zheng X, Sun W, Peng Y, Guo Y, Lu D, et al. Visuoauditory Associative Memory Established with Cholecystokinin Under Anesthesia Is Retrieved in Behavioral Contexts. J Neurosci. 2020;40:2025–37. [DOI] [PubMed] [PMC]

129.

Turrigiano GG, Nelson SB. Homeostatic plasticity in the developing nervous system. Nat Rev Neurosci. 2004;5:97–107. [DOI] [PubMed]

130.

Qin Q, Xu Z, Liu T, Li X, Qiu C, Hu W. CCK-8 enhances acid-sensing ion channel currents in rat primary sensory neurons. Neuropharmacology. 2023;241:109739. [DOI] [PubMed]

131.

Lee SY, Soltesz I. Cholecystokinin: a multi-functional molecular switch of neuronal circuits. Dev Neurobiol. 2011;71:83–91. [DOI] [PubMed] [PMC]

132.

Sadeghi M, Reisi P, Radahmadi M. The effects of CCK-8S on spatial memory and long-term potentiation at CA1 during induction of stress in rats. Iran J Basic Med Sci. 2017;20:1368–76. [DOI] [PubMed] [PMC]

133.

Chen C. Homeostatic regulation of brain functions by endocannabinoid signaling. Neural Regen Res. 2015;10:691–2. [DOI] [PubMed] [PMC]

134.

Eggan SM, Melchitzky DS, Sesack SR, Fish KN, Lewis DA. Relationship of cannabinoid CB1 receptor and cholecystokinin immunoreactivity in monkey dorsolateral prefrontal cortex. Neuroscience. 2010;169:1651–61. [DOI] [PubMed] [PMC]

135.

Marsicano G, Lutz B. Expression of the cannabinoid receptor CB1 in distinct neuronal subpopulations in the adult mouse forebrain. Eur J Neurosci. 1999;11:4213–25. [DOI] [PubMed]

136.

Iball J, Ali AB. Endocannabinoid Release Modulates Electrical Coupling between CCK Cells Connected via Chemical and Electrical Synapses in CA1. Front Neural Circuits. 2011;5:17. [DOI] [PubMed] [PMC]

137.

Mitchell VA, Jeong H, Drew GM, Vaughan CW. Cholecystokinin exerts an effect via the endocannabinoid system to inhibit GABAergic transmission in midbrain periaqueductal gray. Neuropsychopharmacology. 2011;36:1801–10. [DOI] [PubMed] [PMC]

138.

Shen C, Zheng D, Li K, Yang J, Pan H, Yu X, et al. Cannabinoid CB₁ receptors in the amygdalar cholecystokinin glutamatergic afferents to nucleus accumbens modulate depressive-like behavior. Nat Med. 2019;25:337–49. [DOI] [PubMed]

139.

Papagianni EP, Stevenson CW. Cannabinoid Regulation of Fear and Anxiety: an Update. Curr Psychiatry Rep. 2019;21:38. [DOI] [PubMed] [PMC]

140.

Chhatwal JP, Gutman AR, Maguschak KA, Bowser ME, Yang Y, Davis M, et al. Functional interactions between endocannabinoid and CCK neurotransmitter systems may be critical for extinction learning. Neuropsychopharmacology. 2009;34:509–21. [DOI] [PubMed]

141.

Bowers ME, Ressler KJ. Interaction between the cholecystokinin and endogenous cannabinoid systems in cued fear expression and extinction retention. Neuropsychopharmacology. 2015;40:688–700. [DOI] [PubMed] [PMC]

142.

Vargish GA, Pelkey KA, Yuan X, Chittajallu R, Collins D, Fang C, et al. Persistent inhibitory circuit defects and disrupted social behaviour following in utero exogenous cannabinoid exposure. Mol Psychiatry. 2017;22:56–67. [DOI] [PubMed] [PMC]

143.

Vachon-Presseau E. Effects of stress on the corticolimbic system: implications for chronic pain. Prog Neuropsychopharmacol Biol Psychiatry. 2018;87:216–23. [DOI] [PubMed]

144.

Fedoce ADG, Ferreira F, Bota RG, Bonet-Costa V, Sun PY, Davies KJA. The role of oxidative stress in anxiety disorder: cause or consequence? Free Radic Res. 2018;52:737–50. [DOI] [PubMed] [PMC]

145.

Song Q, E S, Zhang Z, Liang Y. Neuroplasticity in the transition from acute to chronic pain. Neurotherapeutics. 2024;21:e00464. [DOI] [PubMed] [PMC]

146.

Wen D, An M, Gou H, Liu X, Liu L, Ma C, et al. Cholecystokinin-8 inhibits methamphetamine-induced neurotoxicity via an anti-oxidative stress pathway. Neurotoxicology. 2016;57:31–8. [DOI] [PubMed]

147.

Gou H, Sun D, Hao L, An M, Xie B, Cong B, et al. Cholecystokinin-8 attenuates methamphetamine-induced inflammatory activation of microglial cells through CCK2 receptor. Neurotoxicology. 2020;81:70–9. [DOI] [PubMed]

148.

Su Y, Liu N, Zhang Z, Li H, Ma J, Yuan Y, et al. Cholecystokinin and glucagon-like peptide-1 analogues regulate intestinal tight junction, inflammation, dopaminergic neurons and α-synuclein accumulation in the colon of two Parkinson's disease mouse models. Eur J Pharmacol. 2022;926:175029. [DOI] [PubMed]

149.

Zhang Z, Li H, Su Y, Ma J, Yuan Y, Yu Z, et al. Neuroprotective Effects of a Cholecystokinin Analogue in the 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine Parkinsonʼs Disease Mouse Model. Front Neurosci. 2022;16:814430. [DOI] [PubMed] [PMC]

150.

Hao L, Shi M, Ma J, Shao S, Yuan Y, Liu J, et al. A Cholecystokinin Analogue Ameliorates Cognitive Deficits and Regulates Mitochondrial Dynamics via the AMPK/Drp1 Pathway in APP/PS1 Mice. J Prev Alzheimers Dis. 2024;11:382–401. [DOI] [PubMed]

151.

Orr HT. Cholecystokinin Activation of Cholecystokinin 1 Receptors: a Purkinje Cell Neuroprotective Pathway. Cerebellum. 2023;22:756–60. [DOI] [PubMed] [PMC]

152.

Rex A, Marsden CA, Fink H. Cortical 5-HT-CCK interactions and anxiety-related behaviour of guinea-pigs: a microdialysis study. Neurosci Lett. 1997;228:79–82. [DOI] [PubMed]

153.

Paudice P, Raiteri M. Cholecystokinin release mediated by 5-HT₃ receptors in rat cerebral cortex and nucleus accumbens. Br J Pharmacol. 1991;103:1790–4. [DOI] [PubMed] [PMC]

154.

Damonte VM, Pomrenze MB, Manning CE, Casper C, Wolfden AL, Malenka RC, et al. Somatodendritic Release of Cholecystokinin Potentiates GABAergic Synapses Onto Ventral Tegmental Area Dopamine Cells. Biol Psychiatry. 2023;93:197–208. [DOI] [PubMed] [PMC]

155.

Hamilton ME, Freeman AS. Effects of administration of cholecystokinin into the VTA on DA overflow in nucleus accumbens and amygdala of freely moving rats. Brain Res. 1995;688:134–42. [DOI] [PubMed]

156.

Raiteri M, Bonanno G, Paudice P, Cavazzani P, Schmid G. Human brain cholecystokinin: release of cholecystokinin-like immunoreactivity (CCK-LI) from isolated cortical nerve endings and its modulation through GABA(B) receptors. J Pharmacol Exp Ther. 1996;278:747–51. [PubMed]

157.

Meyer DK, Krauss J. Dopamine modulates cholecystokinin release in neostriatum. Nature. 1983;301:338–40. [DOI] [PubMed]

158.

Wiesenfeld-Hallin Z, de Araúja Lucas G, Alster P, Xu XJ, Hökfelt T. Cholecystokinin/opioid interactions. Brain Res. 1999;848:78–89. [DOI] [PubMed]

159.

Becker C, Hamon M, Cesselin F, Benoliel JJ. δ₂-opioid receptor mediation of morphine-induced CCK release in the frontal cortex of the freely moving rat. Synapse. 1999;34:47–54. [DOI] [PubMed]

160.

Kim J, Kim JH, Kim Y, Cho H, Hong SK, Yoon YW. Role of spinal cholecystokinin in neuropathic pain after spinal cord hemisection in rats. Neurosci Lett. 2009;462:303–7. [DOI] [PubMed]

161.

Xiang T, Li J, Su H, Bai K, Wang S, Traub RJ, et al. Spinal CCK1 Receptors Contribute to Somatic Pain Hypersensitivity Induced by Malocclusion via a Reciprocal Neuron-Glial Signaling Cascade. J Pain. 2022;23:1629–45. [DOI] [PubMed] [PMC]

162.

Li J, Zhao S, Guo Y, Chen F, Traub RJ, Wei F, et al. Chronic stress induces wide-spread hyperalgesia: The involvement of spinal CCK₁ receptors. Neuropharmacology. 2024;258:110067. [DOI] [PubMed]

163.

Goyal S, Zurek N, Ehsanian R, Goyal S, Jones DT, Shilling M, et al. Visceral pain-related acute actions of cerulein on mouse and human sensory neurons. Mol Pain. 2025;21:17448069251353346. [DOI] [PubMed] [PMC]

164.

Hendrie CA, Shepherd JK, Rodgers RJ. Differential effects of the CCK antagonist, MK-329, on analgesia induced by morphine, social conflict (opioid) and defeat experience (non-opioid) in male mice. Neuropharmacology. 1989;28:1025–32. [DOI] [PubMed]

165.

Legido A, Adler MW, Karkanias C, Geller EB, Bradley E, Greenstein JI, et al. Cholecystokinin potentiates morphine anticonvulsant action through both CCK-A and CCK-B receptors. Neuropeptides. 1995;28:107–13. [DOI] [PubMed]

166.

Wen D, Sun D, Zang G, Hao L, Liu X, Yu F, et al. Cholecystokinin octapeptide induces endogenous opioid-dependent anxiolytic effects in morphine-withdrawal rats. Neuroscience. 2014;277:14–25. [DOI] [PubMed]

167.

Sauter A, Frick W. Determination of cholecystokinin tetrapeptide and cholecystokinin octapeptide sulfate in different rat brain regions by high-pressure liquid chromatography with electrochemical detection. Anal Biochem. 1983;133:307–13. [DOI] [PubMed]

168.

Pavlasevic S, Bednar I, Qureshi GA, Södersten P. Brain cholecystokinin tetrapeptide levels are increased in a rat model of anxiety. Neuroreport. 1993;5:225–8. [DOI] [PubMed]

169.

Ito M, Matsui T, Taniguchi T, Tsukamoto T, Murayama T, Arima N, et al. Functional characterization of a human brain cholecystokinin-B receptor. A trophic effect of cholecystokinin and gastrin. J Biol Chem. 1993;268:18300–5. [PubMed]

170.

Kinlein SA, Wilson CD, Karatsoreos IN. Dysregulated hypothalamic-pituitary-adrenal axis function contributes to altered endocrine and neurobehavioral responses to acute stress. Front Psychiatry. 2015;6:31. [DOI] [PubMed] [PMC]

171.

DʼAgostino G, Lyons DJ, Cristiano C, Burke LK, Madara JC, Campbell JN, et al. Appetite controlled by a cholecystokinin nucleus of the solitary tract to hypothalamus neurocircuit. Elife. 2016;5:e12225. [DOI] [PubMed] [PMC]

172.

Breit S, Kupferberg A, Rogler G, Hasler G. Vagus Nerve as Modulator of the Brain-Gut Axis in Psychiatric and Inflammatory Disorders. Front Psychiatry. 2018;9:44. [DOI] [PubMed] [PMC]

173.

Flood JF, Merbaum MO, Morley JE. The memory enhancing effects of cholecystokinin octapeptide are dependent on an intact stria terminalis. Neurobiol Learn Mem. 1995;64:139–45. [DOI] [PubMed]

174.

Cohen H, Kaplan Z, Matar MA, Buriakovsky I, Bourin M, Kotler M. Different pathways mediated by CCK₁ and CCK₂ receptors: effect of intraperitonal mrna antisense oligodeoxynucleotides to cholecystokinin on anxiety-like and learning behaviors in rats. Depress Anxiety. 2004;20:139–52. [DOI] [PubMed]

175.

Cohen H, Matar MA, Buriakovsky I, Zeev K, Kotler M, Bourin M. Effect of intraperitoneal mRNA antisense-oligodeoxynucleotides to cholecystokinin on anxiety-like and learning behaviors in rats: association with pre-experimental stress. Neuropeptides. 2002;36:341–52. [DOI] [PubMed]

176.

You ZB, Godukhin O, Goiny M, Nylander I, Ungerstedt U, Terenius L, et al. Cholecystokinin-8S increases dynorphin B, aspartate and glutamate release in the fronto-parietal cortex of the rat via different receptor subtypes. Naunyn Schmiedebergs Arch Pharmacol. 1997;355:576–81. [DOI] [PubMed]

177.

Gronier B, Debonnel G. Electrophysiological evidence for the implication of cholecystokinin in the modulation of the N-methyl-D-aspartate response by sigma ligands in the rat CA₃ dorsal hippocampus. Naunyn Schmiedebergs Arch Pharmacol. 1996;353:382–90. [DOI] [PubMed]

178.

Zarrindast M, Khakpai F. The Modulatory Role of Dopamine in Anxiety-like Behavior. Arch Iran Med. 2015;18:591–603. [PubMed]

179.

Huang C, Luo J, Woo SJ, Roitman LA, Li J, Pieribone VA, et al. Dopamine-mediated interactions between short- and long-term memory dynamics. Nature. 2024;634:1141–9. [DOI] [PubMed] [PMC]

180.

Wang H, Wong PT, Spiess J, Zhu YZ. Cholecystokinin-2 (CCK₂) receptor-mediated anxiety-like behaviors in rats. Neurosci Biobehav Rev. 2005;29:1361–73. [DOI] [PubMed]

181.

Hendrie CA, Neill JC, Shepherd JK, Dourish CT. The effects of CCK_A and CCK_B antagonists on activity in the black/white exploration model of anxiety in mice. Physiol Behav. 1993;54:689–93. [DOI] [PubMed]

182.

Ballaz S, Barber A, Fortuño A, Río JD, Martin-Martínez M, Gómez-Monterrey I, et al. Pharmacological evaluation of IQM-95,333, a highly selective CCK_A receptor antagonist with anxiolytic-like activity in animal models. Br J Pharmacol. 1997;121:759–67. [DOI] [PubMed] [PMC]

183.

Schneider R, Osterburg J, Buchner A, Pietrowsky R. Effect of intranasally administered cholecystokinin on encoding of controlled and automatic memory processes. Psychopharmacology (Berl). 2009;202:559–67. [DOI] [PubMed]

184.

Lemaire M, Piot O, Roques BP, Böhme GA, Blanchard JC. Evidence for an endogenous cholecystokininergic balance in social memory. Neuroreport. 1992;3:929–32. [DOI] [PubMed]

185.

Derrien M, Daugé V, Blommaert A, Roques BP. The selective CCK-B agonist, BC 264, impairs socially reinforced memory in the three-panel runway test in rats. Behav Brain Res. 1994;65:139–46. [DOI] [PubMed]

186.

Shlik J, Koszycki D, Bradwejn J. Decrease in short-term memory function induced by CCK-4 in healthy volunteers. Peptides. 1998;19:969–75. [DOI] [PubMed]

187.

Brewer KL, McMillan D, Nolan T, Shum K. Cortical changes in cholecystokinin mRNA are related to spontaneous pain behaviors following excitotoxic spinal cord injury in the rat. Brain Res Mol Brain Res. 2003;118:171–4. [DOI] [PubMed]

188.

Chen XH, Geller EB, Adler MW. CCK_B receptors in the periaqueductal grey are involved in electroacupuncture antinociception in the rat cold water tail-flick test. Neuropharmacology. 1998;37:751–7. [DOI] [PubMed]

189.

Turrigiano G. Homeostatic synaptic plasticity: local and global mechanisms for stabilizing neuronal function. Cold Spring Harb Perspect Biol. 2012;4:a005736. [DOI] [PubMed] [PMC]

190.

Virgo L, Humphries C, Mortimer A, Barnes T, Hirsch S, de Belleroche J. Cholecystokinin messenger RNA deficit in frontal and temporal cerebral cortex in schizophrenia. Biol Psychiatry. 1995;37:694–701. [DOI] [PubMed]

191.

Bachus SE, Hyde TM, Herman MM, Egan MF, Kleinman JE. Abnormal cholecystokinin mRNA levels in entorhinal cortex of schizophrenics. J Psychiatr Res. 1997;31:233–56. [DOI] [PubMed]

192.

Harro J, Marcusson J, Oreland L. Alterations in brain cholecystokinin receptors in suicide victims. Eur Neuropsychopharmacol. 1992;2:57–63. [DOI] [PubMed]

193.

Ballaz SJ, Akil H, Watson SJ. The CCK-system mediates adaptation to novelty-induced stress in the rat: a pharmacological evidence. Neurosci Lett. 2007;428:27–32. [DOI] [PubMed]

194.

Ballaz SJ, Akil H, Watson SJ. The CCK-system underpins novelty-seeking behavior in the rat: gene expression and pharmacological analyses. Neuropeptides. 2008;42:245–53. [DOI] [PubMed] [PMC]

195.

Wunderlich GR, Raymond R, DeSousa NJ, Nobrega JN, Vaccarino FJ. Decreased CCK_B receptor binding in rat amygdala in animals demonstrating greater anxiety-like behavior. Psychopharmacology (Berl). 2002;164:193–9. [DOI] [PubMed]

196.

Hesselink JMK. Rediscovery of Ceruletide, a CCK Agonist, as an Analgesic Drug. J Pain Res. 2020;13:123–30. [DOI] [PubMed] [PMC]

197.

McCleane GJ. The cholecystokinin antagonist proglumide has an analgesic effect in chronic pancreatitis. Pain Clinic. 2003;15:71–3. [DOI]

198.

Lavigne GJ, Hargreaves KM, Schmidt EA, Dionne RA. Proglumide potentiates morphine analgesia for acute postsurgical pain. Clin Pharmacol Ther. 1989;45:666–73. [DOI] [PubMed]

199.

McCleane GJ. The cholecystokinin antagonist proglumide enhances the analgesic effect of dihydrocodeine. Clin J Pain. 2003;19:200–1. [DOI] [PubMed]

200.

Ballaz S. The unappreciated roles of the cholecystokinin receptor CCK(1) in brain functioning. Rev Neurosci. 2017;28:573–85. [DOI] [PubMed]

201.

Panchenko AV, Panchenko AV, Pavlova LE, Timina MF, Cherkashina EV, Kolik LG, et al. Influence of Retrodipeptide Analogue of Cholecystokinin Tetrapeptide (GB-115) and Phenazepam on the Behavior of Rhesus Monkeys under Isolation Conditions. Dokl Biochem Biophys. 2025;520:83–8. [DOI] [PubMed]

202.

Whitebirch AC, Santoro B, Barnett A, Lisgaras CP, Scharfman HE, Siegelbaum SA. Reduced Cholecystokinin-Expressing Interneuron Input Contributes to Disinhibition of the Hippocampal CA2 Region in a Mouse Model of Temporal Lobe Epilepsy. J Neurosci. 2023;43:6930–49. [DOI] [PubMed] [PMC]

203.

Asim M, Qianqian G, Waris A, Wang H, Lai Y, Chen X. Unraveling the role of cholecystokinin in epilepsy: Mechanistic insight into neuroplasticity. Neurochem Int. 2024;180:105870. [DOI] [PubMed]

204.

Löscher W. Single-Target Versus Multi-Target Drugs Versus Combinations of Drugs With Multiple Targets: Preclinical and Clinical Evidence for the Treatment or Prevention of Epilepsy. Front Pharmacol. 2021;12:730257. [DOI] [PubMed] [PMC]

205.

Harikumar KG, Coudrat T, Desai AJ, Dong M, Dengler DG, Furness SGB, et al. Discovery of a Positive Allosteric Modulator of Cholecystokinin Action at CCK1R in Normal and Elevated Cholesterol. Front Endocrinol (Lausanne). 2021;12:789957. [DOI] [PubMed] [PMC]

206.

Agnes RS, Lee YS, Davis P, Ma S, Badghisi H, Porreca F, et al. Structure-activity relationships of bifunctional peptides based on overlapping pharmacophores at opioid and cholecystokinin receptors. J Med Chem. 2006;49:2868–75. [DOI] [PubMed] [PMC]

207.

Ballaz S, Espinosa N, Bourin M. Does endogenous cholecystokinin modulate alcohol intake? Neuropharmacology. 2021;193:108539. [DOI] [PubMed]

208.

Singh L, Field MJ, Hughes J, Menzies R, Oles RJ, Vass CA, et al. The behavioural properties of CI-988, a selective cholecystokinin_B receptor antagonist. Br J Pharmacol. 1991;104:239–45. [DOI] [PubMed] [PMC]

209.

Jenck F, Martin JR, Moreau JL. Behavioral effects of CCK_B receptor ligands in a validated simulation of panic anxiety in rats. Eur Neuropsychopharmacol. 1996;6:291–8. [DOI] [PubMed]

210.

Singh L, Lewis AS, Field MJ, Hughes J, Woodruff GN. Evidence for an involvement of the brain cholecystokinin B receptor in anxiety. Proc Natl Acad Sci U S A. 1991;88:1130–3. [DOI] [PubMed] [PMC]

211.

Bradwejn J, Koszycki D, Couëtoux du Tertre A, van Megen H, den Boer J, Westenberg H. The panicogenic effects of cholecystokinin-tetrapeptide are antagonized by L-365,260, a central cholecystokinin receptor antagonist, in patients with panic disorder. Arch Gen Psychiatry. 1994;51:486–93. [DOI] [PubMed]

212.

Dourish CT, O’Neill MF, Coughlan J, Kitchener SJ, Hawley D, Iversen SD. The selective CCK-B receptor antagonist L-365,260 enhances morphine analgesia and prevents morphine tolerance in the rat. Eur J Pharmacol. 1990;176:35–44. [DOI] [PubMed]