Neuronal Cholecystokinin and Schizophrenia: Pathogenic and Therapeutic Studies

Overview

Journal Psychopharmacology (Berl)

Specialty Pharmacology

Date 1986 Jan 1

PMID 3083460

Citations 5

Authors

C A Tamminga

R L Littman

L D Alphs

T N Chase

G K Thaker

A M Wagman

Affiliations

Soon will be listed here.

Abstract

Neuroleptic-free schizophrenic patients received caerulein, a potent analogue of cholecystokinin octapeptide, in a fixed- and rising-dose schedule. In addition, neuroleptic-treated patients received a single dose of the peptide with a 4-week follow-up. No significant change in mental status was observed after any of these administration schedules. Peak plasma levels of caerulein were noted at 20-30 min after IM administration; at this time no changes in cortical evoked potential were demonstrated. Furthermore, levels of cholecystokinin were not found to be reduced, but were in fact elevated in lumbar cerebrospinal fluid of schizophrenic patients. These data argue against the antipsychotic efficacy of systemic caerulein administration and, because evidence of CNS response to CCK is lacking, suggest that other pharmacologic strategies may be necessary to effectively modify central peptide systems with systemically administered drugs.

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References

ZETLER G . Neuroleptic-like effects of ceruletide and cholecystokinin octapeptide: interactions with apomorphine, methylphenidate and picrotoxin. Eur J Pharmacol. 1983; 94(3-4):261-70. DOI: 10.1016/0014-2999(83)90415-6. View

Roth W, Cannon E . Some features of the auditory evoked response in schizophrenics. Arch Gen Psychiatry. 1972; 27(4):466-71. DOI: 10.1001/archpsyc.1972.01750280034007. View

Pinget M, STRAUS E, Yalow R . Localization of cholecystokinin-like immunoreactivity in isolated nerve terminals. Proc Natl Acad Sci U S A. 1978; 75(12):6324-6. PMC: 393174. DOI: 10.1073/pnas.75.12.6324. View

Skirboll L, Grace A, Hommer D, Rehfeld J, Goldstein M, Hokfelt T . Peptide-monoamine coexistence: studies of the actions of cholecystokinin-like peptide on the electrical activity of midbrain dopamine neurons. Neuroscience. 1981; 6(11):2111-24. DOI: 10.1016/0306-4522(81)90002-6. View

Lucignani G, Porrino L, Tamminga C . Effects of systemically administered cholecystokinin-octapeptide on local cerebral metabolism. Eur J Pharmacol. 1984; 101(1-2):147-51. DOI: 10.1016/0014-2999(84)90041-4. View

Ishibashi S, Oomura Y, Okajima T, Shibata S . Cholecystokinin, motilin and secretin effects on the central nervous system. Physiol Behav. 1979; 23(2):401-3. DOI: 10.1016/0031-9384(79)90386-x. View

Verbanck P, Lotstra F, Gilles C, Linkowski P, Mendlewicz J, Vanderhaeghen J . Reduced cholecystokinin immunoreactivity in the cerebrospinal fluid of patients with psychiatric disorders. Life Sci. 1984; 34(1):67-72. DOI: 10.1016/0024-3205(84)90331-x. View

Pinget M, STRAUS E, Yalow R . Release of cholecystokinin peptides from a synaptosome-enriched fraction of rat cerebral cortex. Life Sci. 1979; 25(4):339-42. DOI: 10.1016/0024-3205(79)90264-9. View

Gerner R, Yamada T . Altered neuropeptide concentrations in cerebrospinal fluid of psychiatric patients. Brain Res. 1982; 238(1):298-302. DOI: 10.1016/0006-8993(82)90801-0. View

10.

Tamminga C, Lewitt P, Chase T . Cholecystokinin and neurotensin gradients in human CSF. Arch Neurol. 1985; 42(4):354-5. DOI: 10.1001/archneur.1985.04060040064013. View

11.

Chase T, Barone P, Bruno G, Cohen S, Juncos J, Knight M . Cholecystokinin-mediated synaptic function and the treatment of neuropsychiatric disease. Ann N Y Acad Sci. 1985; 448:553-61. DOI: 10.1111/j.1749-6632.1985.tb29948.x. View

12.

Cohen S, Knight M, Tamminga C, Chase T . Tolerance to the anti-avoidance properties of cholecystokinin-octapeptide. Peptides. 1983; 4(1):67-70. DOI: 10.1016/0196-9781(83)90168-7. View

13.

MOROJI T, Watanabe N, Aoki N, Itoh S . Antipsychotic effects of ceruletide (caerulein) on chronic schizophrenia. Arch Gen Psychiatry. 1982; 39(4):485-6. DOI: 10.1001/archpsyc.1982.04290040079011. View

14.

Cohen S, Knight M, Tamminga C, Chase T . A comparison of peripheral and central effects of CCK8 on water-reinforced operant responding. Eur J Pharmacol. 1985; 116(3):229-38. DOI: 10.1016/0014-2999(85)90157-8. View

15.

Lotstra F, Verbanck P, Mendlewicz J, Vanderhaeghen J . No evidence of antipsychotic effect of caerulein in schizophrenic patients free of neuroleptics: a double-blind cross-over study. Biol Psychiatry. 1984; 19(6):877-82. View

16.

Beinfeld M, Meyer D, Eskay R, Jensen R, Brownstein M . The distribution of cholecystokinin immunoreactivity in the central nervous system of the rat as determined by radioimmunoassay. Brain Res. 1981; 212(1):51-7. DOI: 10.1016/0006-8993(81)90031-7. View

17.

Dockray G . Immunochemical evidence of cholecystokinin-like peptides in brain. Nature. 1976; 264(5586):568-70. DOI: 10.1038/264568a0. View

18.

Rehfeld J, Kruse-Larsen C . Gastrin and cholecystokinin in human cerebrospinal fluid. Immunochemical determination of concentrations and molecular heterogeneity. Brain Res. 1978; 155(1):19-26. DOI: 10.1016/0006-8993(78)90301-3. View

19.

Markstein R, Hokfelt T . Effect of cholecystokinin-octapeptide on dopamine release from slices of cat caudate nucleus. J Neurosci. 1984; 4(2):570-5. PMC: 6564911. View

20.

Steardo L, Knight M, Tamminga C, Chase T . Products of cholecystokinin (CCK)-octapeptide proteolysis interact with central CCK receptors. Neurosci Lett. 1985; 54(2-3):319-25. DOI: 10.1016/s0304-3940(85)80098-7. View