Cholecystokinin in anxiety

Cholecystokinin (CCK) plays an important role in both the alimentary tract and the central nervous system (CNS). At present it seems to be the most abundant neuropeptide in the CNS. This paper reviews the CCK neuronal system and its interactions with gamma-aminobutyric acid (GABA) and serotonin (5-hydroxytryptamine; 5-HT). In addition, its putative role in anxiety will be discussed on the basis of animal data and studies in healthy volunteers and panic disorder patients. According to these investigations, the CCK4 challenge test fulfills most criteria for an ideal panicogenic agent and evidence has been found that CCKB receptor antagonists might possess anxiolytic properties in man.

[1]  M. Liebowitz Imipramine in the treatment of panic disorder and its complications. , 1985, The Psychiatric clinics of North America.

[2]  M. Bourin,et al.  The cholecystokinin hypothesis of panic and anxiety disorders: a review , 1992, Journal of psychopharmacology.

[3]  J. Champagnat,et al.  The Effects of Cholecystokinin‐8 in the Nucleus Tractus Solitarius , 1985, Annals of the New York Academy of Sciences.

[4]  H. Raper,et al.  Pancreozymin, a stimulant of the secretion of pancreatic enzymes in extracts of the small intestine , 1943, The Journal of physiology.

[5]  G. Woodruff,et al.  Autoradiographical detection of cholecystokinin-A receptors in primate brain using 125I-Bolton Hunter CCK-8 and 3H-MK-329 , 1990, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[6]  W. Nicholson,et al.  Cholecystokinin in human cerebrospinal fluid: concentrations, dynamics, molecular forms and relationship to fasting and feeding in health, depression and alcoholism , 1993, Brain Research.

[7]  M. Raiteri,et al.  Cholecystokinin release mediated by 5‐HT3 receptors in rat cerebral cortex and nucleus accumbens , 1991, British journal of pharmacology.

[8]  P. Mantyh,et al.  Evidence for cholecystokinin-like immunoreactive neurons in the rat medulla oblongata which project to the spinal cord , 1984, Brain Research.

[9]  R. Nesse,et al.  Cholecystokinin-4 and panic. , 1990, Archives of general psychiatry.

[10]  P. Riederer,et al.  Analysis of expression of cholecystokinin in dopamine cells in the ventral mesencephalon of several species and in humans with schizophrenia. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[11]  F. Goodwin,et al.  Demonstration of a putative receptor site for cholecystokinin in rat brain , 1980, Neuropeptides.

[12]  Xiao-Jing Wang,et al.  Cholecystokinin octapeptide antagonized opioid analgesia mediated by μ- and κ- but not δ-receptors in the spinal cord of the rat , 1990, Brain Research.

[13]  G. Sedvall,et al.  CCK peptides and mRNA in the human brain , 1993, Progress in Neurobiology.

[14]  C. Montigny,et al.  Benzodiazepines antagonize cholecystokinin-induced activation of rat hippocampal neurones , 1984, Nature.

[15]  G. Dockray,et al.  Immunochemical evidence of cholecystokinin-like peptides in brain , 1976, Nature.

[16]  C. de Montigny,et al.  Effects of PK 8165, a partial benzodiazepine receptor agonist, on cholecystokinin-induced activation of hippocampal pyramidal neurons: a microiontophoretic study in the rat. , 1985, European journal of pharmacology.

[17]  S. Reines,et al.  A dose-ranging study of the behavioral and cardiovascular effects of CCK-tetrapeptide in panic disorder , 1992, Biological Psychiatry.

[18]  R. G. Hill,et al.  Cholecystokinin and pain. , 1987, Pain and headache.

[19]  C. Montigny,et al.  Cholecystokinin tetrapeptide induces panic-like attacks in healthy volunteers. Preliminary findings. , 1989 .

[20]  B. Costall,et al.  Development of a class of selective cholecystokinin type B receptor antagonists having potent anxiolytic activity. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[21]  T. Hökfelt,et al.  Cholecystokinin peptides produce marked reduction of dopamine turnover in discrete areas in the rat brain following intraventricular injection. , 1980, European journal of pharmacology.

[22]  J. Rehfeld,et al.  N-Terminal fragments of intestinal cholecystokinin: evidence for release of CCK-8 by cleavage on the carboxyl side of Arg74 of proCCK , 1993, Regulatory Peptides.

[23]  E. Griez,et al.  CO2 vulnerability in panic disorder , 1987, Psychiatry Research.

[24]  S. Itoh,et al.  Cholecystokinin tetrapeptide, proglumide and open-field behavior in rats. , 1984, Life sciences.

[25]  J. Bradwejn,et al.  Imipramine antagonism of the panicogenic effects of cholecystokinin tetrapeptide in panic disorder patients. , 1994, The American journal of psychiatry.

[26]  J. Mendels,et al.  A placebo-controlled trial of L-365,260, a CCKB antagonist, in panic disorder , 1995, Biological Psychiatry.

[27]  M. Deschodt-Lanckman,et al.  Cholecystokinin octa- and tetrapeptide degradation by synaptic membranes. I. Evidence for competition with enkephalins for in vitro common degradation pathways , 1981, Peptides.

[28]  S. Freedman,et al.  Measurement of central nervous system activity of systemically administered CCKB receptor antagonists by ex vivo binding. , 1994, European journal of pharmacology.

[29]  H. Westenberg,et al.  Effect of the selective serotonin reuptake inhibitor fluvoxamine on CCK-4 induced panic attacks , 1997, Psychopharmacology.

[30]  T. Silverstone,et al.  Effect of a serotonin and noradrenaline uptake inhibitor in panic disorder: A double-blind comparative study with fluvoxamine and maprotiline. , 1988 .

[31]  W. Verhoeven,et al.  Effect of serotonin uptake inhibitors in anxiety disorders; a double-blind comparison of clomipramine and fluvoxamine. , 1987, International clinical psychopharmacology.

[32]  R. Nesse,et al.  Pentagastrin infusions in patients with panic disorder I. Symptoms and cardiovascular responses , 1994, Biological Psychiatry.

[33]  A. Steggles,et al.  Characterization of Cholecystokinin Binding Sites in Rat Cerebral Cortex Using a 125I‐CCK‐8 Probe Resistant to Degradation , 1983, Journal of neurochemistry.

[34]  R J Gould,et al.  In vivo pharmacology of L-364,718, a new potent nonpeptide peripheral cholecystokinin antagonist. , 1987, The Journal of pharmacology and experimental therapeutics.

[35]  J. Crawley Neurochemical investigation of the afferent pathway from the vagus nerve to the nucleus tractus solitarius in mediating the “satiety syndrome” induced by systemic cholecystokinin , 1985, Peptides.

[36]  S. File,et al.  Benzodiazepines increase preprocholecystokinin messenger RNA levels in rat brain. , 1993, European journal of pharmacology.

[37]  C. Jacquot,et al.  Interaction of cholecystokinin and diazepam: effects on brain monoamines , 1990, Fundamental & clinical pharmacology.

[38]  V. Go,et al.  Release of cholecystokinin from rat cerebral cortex in vivo: role of GABA and glutamate receptor systems , 1987, Brain Research.

[39]  J. Neill,et al.  The effects of CCKA and CCKB antagonists on activity in the black/white exploration model of anxiety in mice , 1993, Physiology & Behavior.

[40]  K. Rasmussen,et al.  The CCK-B antagonist LY288513 blocks effects of diazepam withdrawal on auditory startle. , 1993, Neuroreport.

[41]  J. Fallon,et al.  The Distribution and Some Connections of Cholecystokinin Neurons in the Rat Brain a , 1985, Annals of the New York Academy of Sciences.

[42]  S. Woods,et al.  Noradrenergic neuronal dysregulation in panic disorder: the effects of intravenous yohimbine and clonidine in panic disorder patients , 1992, Acta psychiatrica Scandinavica.

[43]  S. Suomi,et al.  Psychological well-being of primates in captivity. , 1988 .

[44]  C. Marsden,et al.  Effects of BOC-CCK-4 and L 365.260 on cortical 5-HT release in guinea-pigs on exposure to the elevated plus maze , 1994, Neuropharmacology.

[45]  E. Griez,et al.  An analysis of panic symptoms during hypercarbia compared to hypocarbia in patients with panic attacks. , 1991, Journal of affective disorders.

[46]  J. Vanderhaeghen,et al.  New peptide in the vertebrate CNS reacting with antigastrin antibodies , 1975, Nature.

[47]  A. Rex,et al.  Effects of cholecystokinin tetrapeptide and sulfated cholecystokinin octapeptide in rat models of anxiety , 1994, Neuroscience Letters.

[48]  D. Klein,et al.  Blockade by imipramine or desipramine of panic induced by sodium lactate. , 1981, The American journal of psychiatry.

[49]  M. Bourin,et al.  Dose ranging study of the effects of cholecystokinin in healthy volunteers. , 1991, Journal of psychiatry & neuroscience : JPN.

[50]  H. Westenberg,et al.  The panicogenic effects of cholecystokinin-tetrapeptide are antagonized by L-365,260, a central cholecystokinin receptor antagonist, in patients with panic disorder. , 1994, Archives of general psychiatry.

[51]  T. Zahn,et al.  Anxiogenic properties of yohimbine. I. Behavioral, physiological and biochemical measures. , 1992, European archives of psychiatry and clinical neuroscience.

[52]  M. Raiteri,et al.  Release of cholecystokinin in the central nervous system , 1993, Neurochemistry International.

[53]  J. Rehfeld,et al.  Immunochemical studies on cholecystokinin. II. Distribution and molecular heterogeneity in the central nervous system and small intestine of man and hog. , 1978, The Journal of biological chemistry.

[54]  J. Bradwejn,et al.  Cholecystokinin-Tetrapeptide Induces Panic Attacks in Patients with Panic Disorder * , 1990, Canadian journal of psychiatry. Revue canadienne de psychiatrie.

[55]  Steven L. Cohen,et al.  Tolerance to the anti-avoidance properties of cholecystokinin-octapeptide , 1983, Peptides.

[56]  J. Rehfeld,et al.  Distribution of Cholecystokinin‐Like Peptides in the Human Brain , 1982, Journal of neurochemistry.

[57]  J. Rossier,et al.  Inhibitory effect of cholecystokinin octapeptide on neurons in the nucleus tractus solitarius , 1983, Brain Research.

[58]  M. Ticku,et al.  Ethanol enhances [3H]diazepam binding at the benzodiazepine-GABA-receptor-ionophore complex. , 1980, European journal of pharmacology.

[59]  S. Wank,et al.  Molecular cloning, functional expression, and chromosomal localization of the human cholecystokinin type A receptor. , 1993, Annals of the New York Academy of Sciences.

[60]  H. Westenberg,et al.  Anxiogenic effects of pentagastrin in patients with social phobia and healthy controls , 1997, Biological Psychiatry.

[61]  K. Fuxe,et al.  Cholecystokinin-8 increases K(+)-evoked [3H] gamma-aminobutyric acid release in slices from various brain areas. , 1993, European journal of pharmacology.

[62]  P. Keck,et al.  Valproate treatment of panic disorder and lactate-induced panic attacks , 1993, Biological Psychiatry.

[63]  D. La,et al.  Cholecystokinin antagonists--a toxicologic perspective. , 1992 .

[64]  S. Przedborski,et al.  Cholecystokinin octa- and tetrapeptide degradation by synaptic membranes. III. Inactivation of CCK-8 by a phosphoramidon-sensitive endopeptidase , 1984, Peptides.

[65]  B. Costall,et al.  Anxiolytic effects of CCK-B antagonists , 1991, Neuropeptides.

[66]  R. Chang,et al.  Biochemical and pharmacological characterization of an extremely potent and selective nonpeptide cholecystokinin antagonist. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[67]  Scott Wetzler,et al.  m-Chlorophenylpiperazine as a probe of serotonin function , 1991, Biological Psychiatry.

[68]  D. Dahl Systemically administered cholecystokinin affects an evoked potential in the hippocampal dentate gyrus , 1987, Neuropeptides.

[69]  S. Iversen,et al.  Failure of intravenous pentagastrin challenge to induce panic-like effects in rhesus monkeys , 1993, Neuropeptides.

[70]  J. Reeve,et al.  Cholecystokinin--gene structure, and molecular forms in tissue and blood. , 1986, Zeitschrift fur Gastroenterologie.

[71]  S. Wank,et al.  Molecular cloning of the human brain and gastric cholecystokinin receptor: structure, functional expression and chromosomal localization. , 1992, Biochemical and biophysical research communications.

[72]  G. Böhme,et al.  Excitatory effects of cholecystokinin in rat hippocampus: pharmacological response compatible with ‘central’- or B-type CCK receptors , 1988, Brain Research.

[73]  J M Gorman,et al.  Lactate provocation of panic attacks. I. Clinical and behavioral findings. , 1984, Archives of general psychiatry.

[74]  M. Koch,et al.  Cholecystokinin enhances the acoustic startle response in rats. , 1995, Neuroreport.

[75]  J. Palacios,et al.  On the distribution of cholecystokinin receptor binding sites in the human brain: An autoradiographic study , 1987, Synapse.

[76]  R. Payeur,et al.  Replication of action of cholecystokinin tetrapeptide in panic disorder: clinical and behavioral findings. , 1992, The American journal of psychiatry.

[77]  CCK modulates inhibitory synaptic transmission in the solitary complex through CCKB sites. , 1992, Neuroreport.

[78]  C. Tamminga,et al.  Cholecystokinin and neurotensin gradients in human CSF. , 1985, Archives of neurology.

[79]  G. Woodruff,et al.  Pharmacology of a cholecystokinin receptor on 5‐hydroxytryptamine neurones in the dorsal raphe of the rat brain , 1991, British journal of pharmacology.

[80]  G. Woodruff,et al.  Functional role of brain CCK receptors , 1991, Neuropeptides.

[81]  G. Sedvall,et al.  Distribution of cholecystokinin mRNA and peptides in the human brain , 1991, Neuroscience.

[82]  H. Westenberg,et al.  On the significance of cholecystokinin receptors in panic disorder , 1994, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[83]  D. Horwell Development of CCK-B antagonists , 1991, Neuropeptides.

[84]  J. Bradwejn,et al.  Enhanced sensitivity to cholecystokinin tetrapeptide in panic disorder. Clinical and behavioral findings. , 1991, Archives of general psychiatry.

[85]  R. Palmour,et al.  The anxiogenic effects of CCK-4 in monkeys are reduced by CCK-B antagonists, benzodiazepines or adenosine A2 agonists , 1992, European Neuropsychopharmacology.

[86]  M. Bourin,et al.  Evidence for potentiation by CCK antagonists of the effect of cholecystokinin octapeptide in the elevated plus-maze , 1994, Neuropharmacology.

[87]  J. Rehfeld,et al.  Characterization of preprocholecystokinin products in the porcine cerebral cortex. Evidence of different processing pathways. , 1986, The Journal of biological chemistry.

[88]  J. Gorman,et al.  Possible mechanisms for lactate's induction of panic. , 1986, The American journal of psychiatry.

[89]  J. Ballenger,et al.  CSF cholecystokinin concentrations in patients with panic disorder and in normal comparison subjects. , 1992, The American journal of psychiatry.

[90]  Dennis L. Murphy,et al.  Anxiogenic effects of m-CPP in patients with panic disorder: Comparison to caffeine's anxiogenic effects , 1991, Biological Psychiatry.

[91]  L. F. Kolakowski,et al.  The human brain cholecystokinin-B/gastrin receptor. Cloning and characterization. , 1993, The Journal of biological chemistry.

[92]  J. Kelly,et al.  Cholecystokinin as a Potent Excitant of Neurons of the Dentate Gyrus of Rats a , 1985, Annals of the New York Academy of Sciences.

[93]  C. Belzung,et al.  PD135158, a CCK-B antagonist, reduces “state,” but not “trait” anxiety in mice , 1994, Pharmacology Biochemistry and Behavior.

[94]  A. Takashima,et al.  Effect of cholecystokinin tetrapeptide amide on the metabolism of 5-hydroxytryptamine in the rat brain , 1988, Neuropharmacology.

[95]  C. Turkelson,et al.  A cholecystokinin-metabolizing enzyme in rat intestine , 1990, Peptides.

[96]  J. Morley Appetite regulation by gut peptides. , 1990, Annual review of nutrition.

[97]  V. Mutt,et al.  Hormonal polypeptides of the upper intestine. , 1971, The Biochemical journal.

[98]  M. Traub,et al.  Cholecystokinin and anxiety in normal volunteers: an investigation of the anxiogenic properties of pentagastrin and reversal by the cholecystokinin receptor subtype B antagonist L-365,260. , 1995, British journal of clinical pharmacology.

[99]  P. Somogyi,et al.  Different populations of GABAergic neurons in the visual cortex and hippocampus of cat contain somatostatin- or cholecystokinin- immunoreactive material , 1984, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[100]  T. Hökfelt,et al.  Distribution of Cholecystokinin‐like Immunoreactivity in the Nervous System , 1985 .

[101]  S. Dager,et al.  Lactate vulnerability after alprazolam versus placebo treatment of panic disorder , 1991, Biological Psychiatry.

[102]  S. Snyder,et al.  Distinct cholecystokinin receptors in brain and pancreas. , 1980, Proceedings of the National Academy of Sciences of the United States of America.

[103]  M. Verhage,et al.  Characterization of the Release of Cholecystokinin‐8 from Isolated Nerve Terminals and Comparison with Exocytosis of Classical Transmitters , 1991, Journal of neurochemistry.

[104]  C. Marsden,et al.  The influence of 5-hydroxytryptamine re-uptake blockade on CCK receptor antagonist effects in the rat elevated zero-maze. , 1994, European journal of pharmacology.

[105]  M. Randić,et al.  Cholecystokinin octapeptide excites dorsal horn neurons both in vivo and in vitro , 1981, Brain Research.

[106]  J. Harro,et al.  Long-term diazepam treatment produces changes in cholecystokinin receptor binding in rat brain. , 1990, European journal of pharmacology.

[107]  E. Griez,et al.  Panic Symptoms after Inhalation of Carbondioxide , 1984, British Journal of Psychiatry.

[108]  H. Katsumaru,et al.  GABAergic neurons containing the Ca2+-binding protein parvalbumin in the rat hippocampus and dentate gyrus , 1987, Brain Research.

[109]  D. Mcleod,et al.  Effect of fluvoxamine on panic disorder. , 1993, Journal of clinical psychopharmacology.

[110]  G. Woodruff,et al.  The behavioural properties of CI‐988, a selective cholecystokininB receptor antagonist , 1991, British journal of pharmacology.

[111]  T. Insel,et al.  Pharmacologic models of anxiety. , 1983, Comprehensive psychiatry.

[112]  A. Pearse 5-Hydroxytryptophan Uptake by Dog Thyroid ‘C’ Cells, and its Possible Significance in Polypeptide Hormone Production , 1966, Nature.

[113]  S. Hunt,et al.  Separate populations of cholecystokinin and 5-hydroxytryptamine-containing neuronal cells in the rat dorsal raphe, and their contribution to the ascending raphe projections , 1981, Neuroscience Letters.

[114]  M. Toda,et al.  Cholecystokinin antagonism by anthramycin, a benzodiazepine antibiotic, in the central nervous system in mice , 1989, Brain Research.

[115]  B. Roques,et al.  Heterogeneity of CCK-B receptors involved in animal models of anxiety , 1994, Pharmacology Biochemistry and Behavior.

[116]  T. F. Freund,et al.  Subpopulations of GABAergic neurons containing parvalbumin, calbindin D28k, and cholecystokinin in the rat hippocampus , 1991, The Journal of comparative neurology.

[117]  R. Deschenes,et al.  Cloning and sequence analysis of a cDNA encoding rat preprocholecystokinin. , 1984, Proceedings of the National Academy of Sciences of the United States of America.

[118]  C. Montigny,et al.  Antagonism of Cholecystokinin‐induced Activation by Benzodiazepine Receptor Agonists , 1985 .

[119]  C. de Montigny,et al.  Long-term benzodiazepine treatment reduces neuronal responsiveness to cholecystokinin: an electrophysiological study in the rat. , 1988, European Journal of Pharmacology.

[120]  D. Black,et al.  A comparison of fluvoxamine, cognitive therapy, and placebo in the treatment of panic disorder. , 1993, Archives of general psychiatry.

[121]  J. Barrett,et al.  Evaluation of the effects of PD 134308 (CI-988), A CCK-B antagonist, on the punished responding of squirrel monkeys , 1991, Neuropeptides.

[122]  A. Ivy,et al.  A HORMONE MECHANISM FOR GALL-BLADDER CONTRACTION AND EVACUATION , 1928 .

[123]  E G Jones,et al.  Neuropeptide-containing neurons of the cerebral cortex are also GABAergic. , 1984, Proceedings of the National Academy of Sciences of the United States of America.

[124]  R. Kahn,et al.  Behavioral indications for serotonin receptor hypersensitivity in panic disorder , 1988, Psychiatry Research.

[125]  J. Harro,et al.  Evidence that CCKB receptors mediate the regulation of exploratory behaviour in the rat. , 1991, European journal of pharmacology.

[126]  T. Hökfelt,et al.  Distribution patterns of CCK and CCK mRNA in some neuronal and non-neuronal tissues , 1991, Neuropeptides.

[127]  J. Schwartz,et al.  Protection by serine peptidase inhibitors of endogenous cholecystokinin released from brain slices , 1989, Neuroscience.

[128]  M. Palkovits,et al.  Distribution of cholecystokinin (CCK) in the hypothalamus and limbic system of the rat , 1981, Neuropeptides.