Hostname: page-component-78c5997874-j824f Total loading time: 0 Render date: 2024-11-12T22:16:48.293Z Has data issue: false hasContentIssue false
  • English
  • Français

The potential role of cholecystokinin in schizophrenia: review and update

Published online by Cambridge University Press:  16 April 2020

R Payeur ,
MK Nixon ,
M Bourin ,
J Bradwejn  and
JM Legrand
R Payeur
Affiliation:
Département de pharmacologie et GIS Médicament, Faculté de Médecine, 1 rue Gaston Veil, 44035 Nantes Cedex, France
MK Nixon
Affiliation:
Département de pharmacologie et GIS Médicament, Faculté de Médecine, 1 rue Gaston Veil, 44035 Nantes Cedex, France
M Bourin*
Affiliation:
Département de pharmacologie et GIS Médicament, Faculté de Médecine, 1 rue Gaston Veil, 44035 Nantes Cedex, France
J Bradwejn
Affiliation:
St Mary’s Hospital – Mc Gill University, 3830 Lacombe Av, Montréal, Canada
JM Legrand
Affiliation:
Département de pharmacologie et GIS Médicament, Faculté de Médecine, 1 rue Gaston Veil, 44035 Nantes Cedex, France
*
*Correspondence and reprints.
Get access

Summary

The role of the neuropeptide cholecystokinin in schizophrenia has been widely explored because of its modulating action on midbrain dopamine neurons. The recent discovery of more specific receptor subtype cholecystokinin antagonists should be considered as potential treatment for schizophrenia with fewer side effects. This paper reviews cholecystokinin/dopamine interactions in animal and human studies. Clinical trials with cholecystokinin agonists and antagonists in schizophrenia are updated.

Keywords

CholecystokininschizophreniaCCK A receptorCCK B receptordopamine/CCK interaction
Type
Review
Information
European Psychiatry , Volume 8 , Issue 2 , 1993 , pp. 67 - 78
Copyright
Copyright © Elsevier, Paris 1993

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Albus, MAckenheil, MMunch, UNaber, D (1984) Ceruletide: a new drug for the treatment of schizophrenic patients? Arch Gen Psychiatry 41, 528CrossRefGoogle ScholarPubMed
Albus, Mvon Gellhorn, KMunch, UNaber, DAckenheil, M (1986) A double-bind study with ceruletide in chronic schizophrenic patients: biochemical and clinical results. Psychiatr Res 19, 1–7CrossRefGoogle Scholar
Altar, CABoyar, WC (1989) Brain CCK-B receptors mediate the suppression of dopamine release by cholecystokinin. Brain Res 483, 321–326CrossRefGoogle ScholarPubMed
Beinfeld, MCPalkovits, M (1981) Distribution of cholecystokinin in the hypothalamus and limbic system of the rat. Neuropeptides 2, 123–129CrossRefGoogle Scholar
Benardo, LSPrince, DA (1982) Dopamine action on hippocampal pyramidal cells. J Neurosci 2, 415–423CrossRefGoogle ScholarPubMed
Bloom, DMNair, NPVSchwartz, G (1983) CCK-8 in the treatment of schizophrenia. Psychopharmacol Bull 19, 362–363Google Scholar
Bourin, MLe Melledo, JM (1992) Pharmacology of cholecystokinin agonists and antagonists. Eur Neuropsychopharmacol 2, 196–198CrossRefGoogle Scholar
Boza, RARetondo, DJ (1985) Is cholecystokinin therapeutic in chronic schizophrenia? J Clin Psychol 46, 485–486Google ScholarPubMed
Britton, DRYahiro, LCullen, MJKerwin, JFKopecka, HNadzan, AM (1989) Centrally administered CCK-8 suppresses activity in mice by a “peripheral type” CCK receptor. Pharmacol Biochem Behav 34(4), 779–783CrossRefGoogle ScholarPubMed
Chang, RSLLotti, VJMartin, GEChen, TB (1983) Increase in brain 125-I-cholecystokinin receptor binding following chronic haloperidol treatment, intracisternal 6-hydroxydopamine or ventral tegmental lesions. Life Sci 32, 871–878CrossRefGoogle ScholarPubMed
Chiodo, LABunney, BS (1983) Proglumide: selective antagonism of excitatory effects of cholecystokinin in CNS. Science 219, 1449–1451CrossRefGoogle Scholar
Chiodo, LABunney, BS (1987) Population response of midbrain dopaminergic neurons to neuroleptics: further studies on time course and non dopaminergic neuronal influences. J Neurosci 7, 629CrossRefGoogle ScholarPubMed
Crawley, JNStivers, JABlumstein, KSPaul, SM (1985) Cholecystokinin potentiates dopamine-mediated behaviors: evidence for modulation specific to a site of coexistence J Neurosci 5, 1972–1983CrossRefGoogle ScholarPubMed
Crawley, JN (1986) Modulation of mesolimbic dopaminergic behaviors by cholecystokinin. Ann N Y Acad Sci 380–396Google Scholar
Crawley, JN (1991) Cholecystokinin – dopamine interactions. Trends Pharmacol Sci 12, 232–236CrossRefGoogle ScholarPubMed
Dauge, VSteimes, PDerrien, MBeau, NRoques, BPFeger, JL (1989) CCK-8 effects on motivational and emotional states of rats involve CCK-A receptors of the postero-median part of the nucleus accumbens. Pharmacol Biochem Behav 34(1), 157–163CrossRefGoogle Scholar
Ellinwood, EJRockwell, KWagoner, N (1983) Apomorphine behavioral effect is facilitated by dibutyryl/cAMP and inhibited by caerulein. Psychopharmacol Bull 19, 352–354Google Scholar
Emson, PCSandberg, BEB (1983) Cholecystokinin and substance-P in the CNS. Ann Rep Med Chem 18, 31–39Google Scholar
Fallon, JHHicks, RLoughin, SE (1983) The origin of cholecystokinin terminals in the basal forebrain of the rat: evidence from immunofluorescence and retrograde tracing. Neurosci Lett 37, 29–35CrossRefGoogle ScholarPubMed
Farmery, SMOwen, FPoulter, MCrow, TJ (1985) Reduced high affinity cholecystokinin binding in hippocampus and frontal cortex of schizophrenic patients. Life Sci 36, 473–482CrossRefGoogle ScholarPubMed
Ferrier, INRoberts, GWCrow, TJJohnston, ECOwens, DGCLee, YCO’Shaughnessy, DAdrian, TEPolak, JMBloom, SR (1983) Reduced cholecystokinin-like and somatostatin-like immunoreactivity in limbic lobe is associated with negative symptoms in schizophrenia. Life Sci 33, 475–482CrossRefGoogle Scholar
Freeman, ASChiodo, LA (1988) Electrophysiological effects of CCK-8 on identified rat nigrostriatal dopaminergic neurons. Brain Res 439, 266CrossRefGoogle ScholarPubMed
Frey, Ρ (1983) Cholecystokinin octapeptide levels in rat brain are changed after subchronic neuroleptic treatment. Eur J Pharmacol 97, 87–92CrossRefGoogle Scholar
Garver, DLBeinfeld, MCYao, JK (1990) Cholecystokinin, dopamine and schizophrenia. Psychopharmacol Bull 3, 377–380Google Scholar
Gerner, RHYamada, Τ (1982) Altered neuropeptide concentration in cerebrospinal fluid of psychiatric patients. Brain Res 238, 298–302CrossRefGoogle Scholar
Gjerris, ARafaelsen, OJVendsborg, PFahrenkrug, JRehfeld, JF (1984) Vasoactive intestinal polypeptide decreased in CSF in atypical depression. J Affective Disord 7, 325–337CrossRefGoogle ScholarPubMed
Grace, AABunney, BS (1983) Intracellular and extracellular electrophysiology of nigral dopaminergic neurons: identification and characterization. Neurosci 10, 301–315CrossRefGoogle ScholarPubMed
Hamilton, MSheehan, MJDeBelleroche, JHerberg, LG (1984) The cholecystokinin analogue, caerulein, does not modulate dopamine release of dopamine induced locomotor activity in the nucleus accumbens. Neuropeptides 13, 43–50Google Scholar
Harper, AARaper, MS (1943) Pancreozymin, a stimulant of secretion of pancreatic enzymes in extracts of small intestine. J Physiol (Lond) 102, 115–125CrossRefGoogle ScholarPubMed
Hays, SEBeinfeld, MCJensen, RTGoodwin, FKPaul, SM (1980) Demonstration of a putative receptor site for cholecystokinin in rat brain. Neuropeptides 1, 53CrossRefGoogle Scholar
Hays, SEGoodwin, FKPaul, SM (1981) Cholecystokinin receptors are decreased in basal ganglia and cerebral cortex of Huntington’s disease. Brain Res 225, 452CrossRefGoogle ScholarPubMed
Hokfelt, TSkirboll, LRehfeld, JFGoldstein, MMarkey, KDann, O (1980) A subpopulation of mesencephalic dopamine neurons projecting to limbic areas contain a cholecystokinin-like peptide: evidence from immunocystochemistry combined with retrograde tracing. Neurosci 5, 2093CrossRefGoogle Scholar
Hokfelt, TRehfeld, JFSkirboll, LIvemark, BGoldstein, MMarkey, K (1980b) Evidence for coexistence of dopamine and CCK in mesolimbic neurons. Nature 285, 476–478CrossRefGoogle Scholar
Hommer, DWPickar, DRoy, ANinan, PBoronow, JPaul, SM (1984) The effects of ceruletide in schizophrenia. Arch Gen Psychiatry 41, 617–619CrossRefGoogle Scholar
Innis, RBCorrea, FMUhl, GRSchneider, BSnyder, SH (1979) Cholecystokinin octapeptide-like immunoactivity: histochemical localisation in the rat brain. Proc Natl Acad Sci USA 76, 521–525CrossRefGoogle Scholar
Innis, RBBunney, BSCharney, DSPrice, LHGlazer, WMSternberg, DERubin, ALHeninger, GR (1986) Does the cholecystokinin antagonist proglumide possess antipsychotic activity? Psychiatr Res 18, 1–7CrossRefGoogle ScholarPubMed
Itoh, HTanoue, JYagi, GTateyama, MKamisada, MFujii, YTakamiya, MNakajima, S (1982) Clinical study on the psychotropic effects of caerulein: an open clinical trial in chronic schizophrenic patients. Keio J Med 31, 71–95CrossRefGoogle ScholarPubMed
Itoh, HShimazono, ΥKawadita, ΥKudo, ΥSatoh, YTakahashi, R (1986) Clinical evaluation of ceruletide in schizophrenia: a multi-institutional cooperative double-blind controlled study. Psychopharmacol Bull 22, 123–128Google ScholarPubMed
Ivy, ACOldberg, E (1928) Hormone mechanism for gallblader contraction. Am J Physiol 85, 381–383Google Scholar
Kerwin, RRobinson, PStephenson, J (1992) Distribution of CCK binding sites in human hippocampal formation and their alteration in schizophrenia: a postmortem autoradiographic study. Psychol Med 22, 37–43CrossRefGoogle Scholar
Kleinman, JEGovoni, SMemo, MHanbauer, IWyatt, RJ (1982) Cholecystokinin and calmodulin in schizophrenic brains. 37th Annual Meeting of the Society of Biological Psychiatry May, Toronto, Abstract, 98, 129Google Scholar
Koshikawa, NKikuchi de Beltran, KSaigusa, TKobayashi, MStephenson, JD (1991) Cholecystokinin octapeptide and caerulein injection into the dorsomedial nucleus accumbens potentiate apomorphine-induced jaw movements in rats. Eur J Pharmacol 209, 75–80CrossRefGoogle ScholarPubMed
Lotstra, FVerbanck, PMendlewicz, JVanderhaeghen, JJ (1984)No evidence of antipsychotic effect of coerulein in schizophrenic patients free of neuroleptics: a double-blind crossover study. Biol Psychiatry 19, 877–882Google Scholar
Marshall, FHBarnes, SHughes, JWoodruff, GNHunter, JC (1991) Cholecystokinin modulates the release of dopamine from the anterior and posterior nucleus accumbens by two different mechanisms. J Neurochem 56, 917–922CrossRefGoogle ScholarPubMed
Mattes, JAHom, WRochford, JM (1985) A high-dose, double-blind study of ceruletide in the treatment of schizophrenia. Am J Psychiatry 142, 1482–1484Google ScholarPubMed
Mattes, JAHom, WRochford, JMOrlosky, M (1985) Ceruletide for schizophrenia: a double-blind study. Biol Psychiatry 20, 533–538CrossRefGoogle ScholarPubMed
Meltzer, HYStahl, SM (1976) The dopamine hypothesis of schizophrenia. Schizophren Bull 19–76CrossRefGoogle ScholarPubMed
Montgomery, SAGreen, MCD (1988) The use of cholecystokinin in schizophrenia: a review. Psychol Med 18, 593–603CrossRefGoogle ScholarPubMed
Moran, THRobinson, PhGoldrick, MMcHugh, Pr (1986) Two brain CCK receptors: implications for behavioral action. Brain Res 362, 1175–1179CrossRefGoogle Scholar
Moroji, TWatanabe, NAoke, NItoh, S (1982) Antipsychotic effects of caerulein, as decapeptide chemically related to cholecystokinin octapeptide in schizophrenia. Int Pharmacopsychiatry 17, 255–273Google Scholar
Moroji, TItoh, K (1985) Antipsychotic effects of ceruletide in chronic schizophrenia. Ann NY Acad Sci 448, 518–533CrossRefGoogle ScholarPubMed
Mutt, VJorpes, JE (1968) Structure of porcine cholecystokinin pancreozymin. Cleavage with thrombin and trypsin. Eur J Biochem 47, 156–162CrossRefGoogle Scholar
Nair, NPVBloom, DMNesteros, JN (1982) Cholecystokinin appears to have antipsychotic properties. Prog Neuropsychopharm & Biol Psychiatry 8, 711–714CrossRefGoogle Scholar
Nair, NPVBloom, DMNesteros, JNSchwartz, G (1983) Therapeutic efficacy of cholecystokinin in neuroleptic resistant schizophrenic subjects. Psychopharmacol Bull 19, 134–136Google Scholar
Nair, NPVLal, SBloom, DM (1985) Cholecystokinin peptides, dopamine and schizophrenia – a review. Prog Neuro-Psychopharm & Biol Psychiatry 9, 515–524CrossRefGoogle ScholarPubMed
Nair, NPVBloom, DMLal, SDebonnel, GSchwartz, GMosticyan, S (1985) Clinical and neuroendocrine studies with cholecystokinin peptides. Ann NY Acad Sci 448, 535–541CrossRefGoogle ScholarPubMed
Nair, NPVLal, SBloom, DM (1986) Cholecystokinin and schizophrenia. Prog Brain Res 65, 237–258CrossRefGoogle Scholar
Panza, GMonzani, ESacerdote, ΡPenati, GPanerai, AE (1992) Beta-endorphin, VIP, and CCK in peripheral blood mononuclear cells from healthy subjects and from drug-free and haloperidol-treated schizophrenic patients. Acta Psychiatr Scand 85, 207–210CrossRefGoogle Scholar
Passalo, EDebas, HOldendorf, WYamada, Τ (1982) Rapid appearance of ICV administered neuropeptides in the peripheral circulation. Brain Res 241, 335–340Google Scholar
Perry, RHDockray, GJDimaline, RPerry, EKBlessed, GTomlinson, BE (1981) Neuropeptides in Alzheimer’s disease, depression and schizophrenia. J Neuro Sci 51, 465–472CrossRefGoogle Scholar
Peselow, EAngrist, BSudilovsky, ACorwin, JSiekriske, JTrent, FRostresen, J (1987) Double-blind controlled trials of CCK-8 in neuroleptic-refractory schizophrenia. Psychopharmacol Bull 91, 80–8 4CrossRefGoogle ScholarPubMed
Pinget, MStraus, EYalow, RS (1979) Release of cholecystokinin peptides from a synaptosome-enriched fraction of rat cerebral cortex. Life Sci 25, 339–342CrossRefGoogle ScholarPubMed
Rafaelsen, OJGjerris, A (1985) Neuropeptides in the CSF in psychiatric disorders. Prog Neuropsychopharmacol Biol Psychiatry 9, 533–538CrossRefGoogle ScholarPubMed
Rasmussen, KStockton, MECzachura, JFHowbert, JJ (1991) Cholecystokinin and schizophrenia: the selective CCK-B anatagonist LY262691 decreases midbrain dopamine unit activity. Eur J Pharmacol 209, 135–138CrossRefGoogle Scholar
Rehfeld, JF (1978) Immunochemical studies on cholecystokinin: distribution and molecular heterogeneity in the CNS and small intestine of man and hog. J Biol Chem 253, 4022Google Scholar
Rehfeld, JF (1992) Cholecystokinin expression in the central nervous system. J Eur Neuropsychopharmacol 2, 189–191CrossRefGoogle Scholar
Rehfeld, JFGolterman, R (1979) Immunochemical evidence of cholecystokinin tetrapeptide in hog brain. J Neurochem 32, 1339–1341CrossRefGoogle Scholar
Saito, AGoldfine, IDWilliams, JA (1981) Characterisation of receptors for cholecystokinin related peptides in mouse cerebral cortex. J Neurochem 37, 483CrossRefGoogle Scholar
Schneider, LHAlpert, JEIversen, SD (1983) Modulation of mesolimbic dopamine: antagonism of amphetamine-stimulated behaviors. Peptides 4, 749–753CrossRefGoogle ScholarPubMed
Skirboll, LGrace, AAHomer, DWRehfeld, JFGoldstein, MHokfelt, TBunney, BS (1981) Peptidemonoamine coexistence: studies on the actions of cholecystokinin-like peptides on the electrical activity of midbrain dopamine neurons. Neurosci 6, 2111CrossRefGoogle ScholarPubMed
Tamminga, CALittman, RLAlphs, LD (1986) Cholecystokinin: a neuropeptide in the treatment of schizophrenia. Psychopharmacol Bull 22, 129–131Google ScholarPubMed
Tamminga, CALittman, RLAlphs, LDChase, TNTuaker, GKWagman, AM (1986) Neuronal cholecystokinin and schizophrenia: pathogenic and therapeutic studies. Psychopharmacol Bull 88, 387–391Google ScholarPubMed
Vaccarino, FJRankin, J (1989) Nucleus accumbens CCK can either attenuate or potentiate amphetamine-induced locomotor activity: evidence for rostral-caudal differences in accumbens CCK function. Behav Neurosci 103, 831CrossRefGoogle ScholarPubMed
Van Ree, JMGaffori, ODe Wield, D (1983) In rats, the behavioral profile of CCK-8 related peptides resembles that of antipsychotic agents. Eur J Pharmacol 93, 63–78CrossRefGoogle ScholarPubMed
Van Ree, JMVerhoeven, WMBrouvers, GJDe Wied, D (1984) Ceruletide resembles antipsychotics in rats and schizophrenics. Neuropsychobiol 12, 4–8CrossRefGoogle Scholar
Vanderhaeghen, JJCrawley, JN (1985) Neuronal cholecystokinin. Ann NY Acad Sci 448Google Scholar
Vanderhaeghen, JJSigneau, JCGepts, W (1975) New peptide in the vertebrate CNS reacting with antigastrin antibodies. Nature 257, 604–605CrossRefGoogle ScholarPubMed
Vanderhaeghen, JJLotstra, FDeMey, JGiles, (1980) lmmunohistochemical localization of cholecystokinin and gastrin like peptide in the brain and hypophysis of the rat. Proc Natl Acad Sci USA 77, 1190–1980CrossRefGoogle Scholar
Vasar, EAllikmets, LRyzhov, IPrakhye, ISoosaar, AMirzayev, S (1988) Intraspecies differences in the behavioural effects of caerulein, an agonist of CCK-8 receptors, in mice and rats. Bull Exp Biol Med 105, 168–171Google Scholar
Vasar, EHarro, JLang, APôld, ASoosaar, A (1991) Differential involvement of CCK-A and CCK-B receptors in the regulation of locomotor activity in the mouse. Psychopharmacol 105, 393–399CrossRefGoogle ScholarPubMed
Verbank, PMPLotstra, FGilles, CLinkowski, PMendlewicz, JVanderhaeghen, JJ ( 1983) Reduced cholecystokinin immuno-reactivity in the CFS of patients with psychiatric disorders. Life Sci 34, 67–72CrossRefGoogle Scholar
Verhoeven, WMAWestenberg, HGMVan Ree, JMA (1986) A comparative study on the antipsychotic properties of desenkephalin-endorphin and ceruletide in schizophrenic patients. Acta Psychiatr Scand 73, 372–382CrossRefGoogle ScholarPubMed
Voigt, MWang, RYWestfall, TC (1986)Cholecystokinin octopeptides alter the release of encogenous dopamine from the rat nucleus accumbens in vitro. J Pharmacol Exp Ther 237, 147–153Google Scholar
Wang, RYWhite, FJVoigt, MM (1984) Cholecystokinin, dopamine and schizophrenia. Trends Pharmacol Sci 5, 436–438CrossRefGoogle Scholar
Wang, RYHU, XT (1986) Does cholecystokinin potentiate dopamine action in the nucleus accumbens? Brain Res 380, 363–367CrossRefGoogle ScholarPubMed
Wang, RY (1988) Cholecystokinin, dopamine and schizophrenia: recent progress and current problems. Ann NY Acad Sci 537, 362–379CrossRefGoogle ScholarPubMed
Weiss, FHorvitz, JCMann, JGEttenberg, A (1986) Intraaccumbens injections of CCK block the hyperlocomotion and potentiate the stereotypy produced by amphetamine. Soc Neurosci Abstract 440. 10Google Scholar
Wennogle, LSteel, DJPetrack, B (1985) Characterization of central cholecystokinin receptors using a radiodinated octapeptide probe. Life Sci 36, 1485–1492CrossRefGoogle Scholar
White, FJWang, RY (1983) Differential effects of classical and atypical antipsychotic drugs on A-9 and A-10 dopamine neurons. Science 221,1054–1057CrossRefGoogle Scholar
White, FJWang, RY (1984a) Pharmacological characterization of dopamine autoreceptors in the rat Ventral Tegmental Area: microiontophoretic studies. J Pharmacol Exp ther 231, 215–219Google Scholar
White, FJWang, RY (1984b) Interactions of cholecystokinin octapeptide and dopamine on nucleus accumbens neurons, Brain Res 300, 161–166CrossRefGoogle Scholar
Whiteford, HAStedman, TJWelham, JCsernansky, JGPond, SM (1992) Placebo-controlled double-blind study of the effects of proglumide in the treatment of schizophrenia. J Clin Psychopharmacol 5, 337-340Google Scholar
Widerlov, EKalivas, PWLewis, MHPrange, AJBreese, GR (1983) Influence of cholecystokinin on central monoaminergic pathways. Reg Pep 6, 99–109CrossRefGoogle ScholarPubMed
Yamagani, SHirayama, EMori, KKawakita, Υ (1986) Dose effect relationship of ceruletide in the treatment of neurolptic-resistant schizophrenia. Curr Ther Res 39, 1044–1053Google Scholar
Zarbin, MAInnis, RBWamsley, JKSnyder, SHHKuhar, MJ (1981) Autoradiographic localization of CCK receptors in guinea pig brain. Eur J Pharmacol 71, 349–350CrossRefGoogle ScholarPubMed
Zetler, G (1985) Neuropharmacological profile of cholecystokinin-like peptides. Ann NY Acad Sci 448, 448–469CrossRefGoogle ScholarPubMed
Zhang, JChiodo, LAFreeman, AS (1991) Effects of the CCK-A receptor antagonist CR 1409 on the activity of rat midbrain dopamine neurons. Peptides 12, 339CrossRefGoogle ScholarPubMed
Submit a response

Comments

No Comments have been published for this article.