Social Isolation of Rats Increases the Density of Cholecystokinin Receptors in the Frontal Cortex and Abolishes the Anti-exploratory Effect of Caerulein

Overview

Journal Naunyn Schmiedebergs Arch Pharmacol

Specialty Pharmacology

Date 1993 Jul 1

PMID 8397343

Citations 10

Authors

E Vasar

E Peuranen

J Harro

A Lang

L Oreland

P T Mannisto

Affiliations

Soon will be listed here.

Abstract

The role of cholecystokinin (CCK) receptors in the development of anxiety caused by social isolation of rats was studied using the elevated plus-maze and receptor binding techniques. The isolation of male Wistar rats significantly reduced their exploratory activity in the elevated plus-maze compared with that of rats kept in groups of four. Caerulein (0.1-5 micrograms/kg s.c.), an agonist at CCK receptors, only at the highest dose (5 micrograms/kg) significantly decreased the exploratory behaviour of rats housed in groups, but not in the isolated rats. By contrast, small doses of caerulein (0.1-0.5 microgram/kg) even tended to increase the behavioural activity of isolated rats in the plus-maze test. In parallel to the behavioural changes, isolation of the rats increased the number of [3H]pCCK-8 binding sites in the frontal cortex, but not in the other forebrain structures (the mesolimbic area, striatum and hippocampus). Isolation did not affect the density of benzodiazepine receptors in the frontal cortex. In conclusion, the isolation of rats for 7 days produced anxiogenic-like effect on the behaviour of rats and increased the number of CCK receptors in the frontal cortex without affecting benzodiazepine receptors.

Citing Articles

The neuropeptide Drosulfakinin regulates social isolation-induced aggression in .

Agrawal P, Kao D, Chung P, Looger L J Exp Biol. 2020; 223(Pt 2).

PMID: 31900346 PMC: 7033730. DOI: 10.1242/jeb.207407.

Cholecystokinin and psychiatric disorders : role in aetiology and potential of receptor antagonists in therapy.

Shlik J, Vasar E, Bradwejn J CNS Drugs. 2013; 8(2):134-52.

PMID: 23338219 DOI: 10.2165/00023210-199708020-00005.

Neuropeptide regulation of fear and anxiety: Implications of cholecystokinin, endogenous opioids, and neuropeptide Y.

Bowers M, Choi D, Ressler K Physiol Behav. 2012; 107(5):699-710.

PMID: 22429904 PMC: 3532931. DOI: 10.1016/j.physbeh.2012.03.004.

Targeted invalidation of CCK2 receptor gene induces anxiolytic-like action in light-dark exploration, but not in fear conditioning test.

Raud S, Innos J, Abramov U, Reimets A, Koks S, Soosaar A Psychopharmacology (Berl). 2005; 181(2):347-57.

PMID: 15830228 DOI: 10.1007/s00213-005-2255-x.

Enhanced cortical extracellular levels of cholecystokinin-like material in a model of anticipation of social defeat in the rat.

Becker C, Thiebot M, Touitou Y, Hamon M, Cesselin F, Benoliel J J Neurosci. 2001; 21(1):262-9.

PMID: 11150343 PMC: 6762450.

References

Markwell M, Haas S, Bieber L, Tolbert N . A modification of the Lowry procedure to simplify protein determination in membrane and lipoprotein samples. Anal Biochem. 1978; 87(1):206-10. DOI: 10.1016/0003-2697(78)90586-9. View

Hokfelt T, Skirboll L, Rehfeld J, Goldstein M, Markey K, DANN O . A subpopulation of mesencephalic dopamine neurons projecting to limbic areas contains a cholecystokinin-like peptide: evidence from immunohistochemistry combined with retrograde tracing. Neuroscience. 1980; 5(12):2093-124. DOI: 10.1016/0306-4522(80)90127-x. View

Blanc G, Herve D, Simon H, Lisoprawski A, Glowinski J, Tassin J . Response to stress of mesocortico-frontal dopaminergic neurones in rats after long-term isolation. Nature. 1980; 284(5753):265-7. DOI: 10.1038/284265a0. View

Harro J, Vasar E . Evidence that CCKB receptors mediate the regulation of exploratory behaviour in the rat. Eur J Pharmacol. 1991; 193(3):379-81. DOI: 10.1016/0014-2999(91)90156-k. View

Rattray M, Singhvi S, Wu P, Andrews N, File S . Benzodiazepines increase preprocholecystokinin messenger RNA levels in rat brain. Eur J Pharmacol. 1993; 245(2):193-6. DOI: 10.1016/0922-4106(93)90129-w. View

Crespi F, Wright I, Mobius C . Isolation rearing of rats alters release of 5-hydroxytryptamine and dopamine in the frontal cortex: an in vivo electrochemical study. Exp Brain Res. 1992; 88(3):495-501. DOI: 10.1007/BF00228179. View

Barrett R, Steffey M, Wolfram C . Type-A cholecystokinin binding sites in cow brain: characterization using (-)-[3H]L364718 membrane binding assays. Mol Pharmacol. 1989; 36(2):285-90. View

Somogyi P, Hodgson A, Smith A, Nunzi M, Gorio A, Wu J . Different populations of GABAergic neurons in the visual cortex and hippocampus of cat contain somatostatin- or cholecystokinin-immunoreactive material. J Neurosci. 1984; 4(10):2590-603. PMC: 6564707. View

Moran T, Robinson P, Goldrich M, McHugh P . Two brain cholecystokinin receptors: implications for behavioral actions. Brain Res. 1986; 362(1):175-9. DOI: 10.1016/0006-8993(86)91413-7. View

10.

Bradwejn J, De Montigny C . Benzodiazepines antagonize cholecystokinin-induced activation of rat hippocampal neurones. Nature. 1984; 312(5992):363-4. DOI: 10.1038/312363a0. View

11.

Kharro I, Pyld M, Vasar E, ALLIKMETS L . [The participation of CCK-8-ergic mechanisms in the regulation of emotional behavior in rodents]. Zh Vyssh Nerv Deiat Im I P Pavlova. 1989; 39(5):877-83. View

12.

Harro J, Pold M, Vasar E . Anxiogenic-like action of caerulein, a CCK-8 receptor agonist, in the mouse: influence of acute and subchronic diazepam treatment. Naunyn Schmiedebergs Arch Pharmacol. 1990; 341(1-2):62-7. DOI: 10.1007/BF00195059. View

13.

Bradwejn J, Koszycki D, Meterissian G . Cholecystokinin-tetrapeptide induces panic attacks in patients with panic disorder. Can J Psychiatry. 1990; 35(1):83-5. DOI: 10.1177/070674379003500115. View

14.

Harro J, Lang A, Vasar E . Long-term diazepam treatment produces changes in cholecystokinin receptor binding in rat brain. Eur J Pharmacol. 1990; 180(1):77-83. DOI: 10.1016/0014-2999(90)90594-v. View

15.

Harro J, Vasar E . Cholecystokinin-induced anxiety: how is it reflected in studies on exploratory behaviour?. Neurosci Biobehav Rev. 1991; 15(4):473-7. DOI: 10.1016/s0149-7634(05)80134-4. View

16.

Harro J, Marcusson J, Oreland L . Alterations in brain cholecystokinin receptors in suicide victims. Eur Neuropsychopharmacol. 1992; 2(1):57-63. DOI: 10.1016/0924-977x(92)90037-9. View

17.

Handley S, Mithani S . Effects of alpha-adrenoceptor agonists and antagonists in a maze-exploration model of 'fear'-motivated behaviour. Naunyn Schmiedebergs Arch Pharmacol. 1984; 327(1):1-5. DOI: 10.1007/BF00504983. View

18.

Singh L, Lewis A, Field M, Hughes J, Woodruff G . Evidence for an involvement of the brain cholecystokinin B receptor in anxiety. Proc Natl Acad Sci U S A. 1991; 88(4):1130-3. PMC: 50970. DOI: 10.1073/pnas.88.4.1130. View

19.

Harro J, Kiivet R, Lang A, Vasar E . Rats with anxious or non-anxious type of exploratory behaviour differ in their brain CCK-8 and benzodiazepine receptor characteristics. Behav Brain Res. 1990; 39(1):63-71. DOI: 10.1016/0166-4328(90)90121-t. View

20.

Itoh S, Takashima A, Katsuura G . Effect of cholecystokinin tetrapeptide amide on the metabolism of 5-hydroxytryptamine in the rat brain. Neuropharmacology. 1988; 27(4):427-31. DOI: 10.1016/0028-3908(88)90152-9. View