Abstract
To investigate whether isolation rearing alters 5-hydroxytryptamine2C (5-HT2C) receptors, the effect of the serotonin agonistm-chlorophenylpiperazine (mCPP) was examined on elevated plus-maze behaviour, plasma corticosterone and brain 5-HT2C receptor protein levels in rats. There was no distinction between behaviour or corticosterone levels in drug-free isolates or socially housed rats exposed to the elevated plus-maze. The anxiogenic response tomCPP (decrease in open arm entry and time and an increase in stretch attend postures) on the elevated plus-maze was greater in isolation than in socially reared controls without any concomitant difference in the hypolocomotor effect ofmCPP in the two groups.mCPP produced a greater elevation in plasma corticosterone in isolates than in group-housed controls. Hippocampal 5-HT2C receptor protein-like immunoreactive levels were significantly lower followingmCPP than saline only in rats reared in isolation. These results indicate that increased 5-HT2C receptor responsiveness accompanies isolation-rearing and may contribute to the enhanced response to stress and the increased neophobia seen in this animal model of trait anxiety/depression. In isolation reared rats, rapid down-regulation of supersensitive 5-HT2C receptors may occur in the hippocampus following 5-HT agonist challenge.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Beckett S, Marsden CA (1995) Computer analysis and quantification of periaqueductal grey-induced defence behaviour. J Neurosci Methods 58:157–161
Bickerdike MJ, Wright IA, Marsden CA (1993) Social isolation attenuates rat forebrain 5-HT release induced by KC1 stimulation and exposure to a novel environment. Behav Pharmacol 4:231–236
Chaouloff F (1993) Physiopharmacological interactions between stress hormones and central serotonergic systems. Brain Res Rev 18:1–32
Einon DF, Morgan MJ (1978) Early social isolation produces' enduring hyperactivity in the rat, but no effect on spontaneous alteration. Q J Exp Psychol 30:151–156
File SE, Velluchi SV (1978) Studies on the role of ACTH and of 5-HT in anxiety, using an animal model. J Pharm Pharmacol 30:105–110
File SE, Zangrossi H, Sanders FL, Mabbutt PS (1994) Raised corticosterone in the rat after exposure to the elevated plus-maze. Psychopharmacology 113:543–546
Fulford AJ, Butler S, Heal DJ, Kendall DA, Marsden CA (1994) Evidence for altered a2-adrenoceptor function following isolation-rearing in the rat. Psychopharmacology 116:183–190
Gentsch C, Lichtsteiner M, Feer H (1981) Locomotor activity, defecation score and corticosterone levels during an openfield exposure: a comparison among individually and group-housed rats, and gentically selected rat lines. Physiol Behav 27:183–186
Gibson EL, Barnfield AMC, Curzon G (1994) Evidence thatmCPP-induced anxiety in the plus-maze is mediated by post-synaptic 5-HT2C receptors but not by sympathomimetic effects. Neuropharmacology 33:457–465
Greco AM, Gambadella P, Sticchi R, D'Aponte D, Di Renzo G, De Franciscis P (1989) Effect of individual housing on circadian rhythms of adult rats. Physiol Behav 45:363–366
Greenough WT, Madden TC, Fleischmann TB (1972) Effect of isolation, daily handling and enriched rearing on maze learning. Psychon Sci 27:279–280
Holson RR, Scallet AC, Ali SF, Turner BB (1991) “Isolation stress” revisited: isolation-rearing effects depend on animal care methods. Physiol Behav 49:1107–1118
Jones GH, Marsden CA, Robbins TW (1989) Isolation-rearing retards the acquisition opf schedule-induced polydipsia in rats. Physiol Behav 45:71–78
Jones GH, Marsden CA, Robbins TW (1990) Increased sensitivity to amphetamine and reward-related stimuli following social isolation in rats; possible disruption of dopamine dependent mechanisms of nucleus accumbens. Psychopharmacology 102:364–372
Juraska JM, Henderson C, Muller J (1984) Differential rearing experience, gender and radial maze performance. Dev Psychobiol 17:209–215
Kalen P, Rosengren E, Lindvall O, Bjorklund A (1989) Hippocampal noradrenaline and serotonin release over 24 hours as measured by the dialysis technique in freely moving rats: correlation to behavioural activity state, effect of handling and tail pinch. Eur J Neurosci 1:181–186
Kennett GA (1992) 5-HT1C receptor antagonists have anxiolytic-like actions in the rat social interaction model. Psychopharmacology 107:379–384
Kennett GA, Curzon G (1988) Evidence thatmCPP may have behavioural effects mediated by central 5-HT1C receptors. Br J Pharmacol 94:137–147
Kennett GA, Bailey F, Piper DC, Blackburn TP (1995) Effect of SB 200646A, a 5-HT2C5-HT2B receptor antagonist, in 2 conflict models of anxiety. Psychopharmacology 118:178–182
Parker V, Morinan A (1986) The socially-isolated rat as a model for anxiety. Neuropharmacology 25:663–664
Rocha B, Rigo M, Di SG, Sandner G, Hoyer D (1994) Chronic mianserin or eltoprazine treatment in rats: effects on the elevated plus-maze test and on limbic 5-HT2C receptor levels. Eur J Pharmacol 262:125–131
Sahakian BJ, Robbins TW, Morgan MJ, Iversen SD (1975) The effects of psychomotor stimulants on stereotypy and locomotor activity in socially deprived and control rats. Brain Res 84:195–205
Sharma A, Topham IA, Fone KCF (1994) Effect of the 5,7-dihydroxytryptamine on 5-HT2C receptor protein-like immunoreactivity in the rat brain and spinal cord. Br J Pharmacol 111:150P
Shepherd JK, Grewal SS, Fletcher A, Bill DJ, Dourish CT (1994) Behavioural and pharmacological characterisation of the elevated “zero-maze” as an animal model of anxiety. Psychopharmacology 116:56–64
Walsh RN, Cummins RA (1976) The open field test: a critical review. Psychol Bull 83:482–504
Whitton P, Curzon G (1990) Anxiogenic-like effect of infusing 1-(3-chlorophenyl)piperazine (mCPP) into the hippocampus. Psychopharmacology 100:138–140
Wright IK, Ismail H, Upton N, Marsden CA (1991a) Effect of isolation rearing on 5-HT agonist-induced responses in the rat. Psychopharmacology 105:259–263
Wright IK, Upton N, Marsden CA (1991b) Resocialisation of isolation-reared rats does not alter the anxiogenic profile on the elevated x-maze model of anxiety. Physiol Behav 50:1129–1132
Wright IA, Upton N, Marsden CA (1992) Effect of established and putative anxiolytics on extracellular 5-HT and 5-HIAA in the ventral hippocampus of rats during behaviour on the elevated X-maze. Psychopharmacology 109:338–346
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Fone, K.C.F., Shalders, K., Fox, Z.D. et al. Increased 5-HT2C receptor responsiveness occurs on rearing rats in social isolation. Psychopharmacology 123, 346–352 (1996). https://doi.org/10.1007/BF02246645
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF02246645