, Volume 123, Issue 4, pp 346–352 | Cite as

Increased 5-HT2C receptor responsiveness occurs on rearing rats in social isolation

  • K. C. F. Fone
  • K. Shalders
  • Z. D. Fox
  • R. Arthur
  • C. A. Marsden
Original Investigation


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.

Key words

5-Hydroxytryptamine2C receptors Social isolation Elevated plus-maze Anxiety Corticosterone Serotonin 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Beckett S, Marsden CA (1995) Computer analysis and quantification of periaqueductal grey-induced defence behaviour. J Neurosci Methods 58:157–161Google Scholar
  2. 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 4:231–236Google Scholar
  3. Chaouloff F (1993) Physiopharmacological interactions between stress hormones and central serotonergic systems. Brain Res Rev 18:1–32Google Scholar
  4. Einon DF, Morgan MJ (1978) Early social isolation produces' enduring hyperactivity in the rat, but no effect on spontaneous alteration. Q J Exp Psychol 30:151–156Google Scholar
  5. File SE, Velluchi SV (1978) Studies on the role of ACTH and of 5-HT in anxiety, using an animal model. J Pharm Pharmacol 30:105–110Google Scholar
  6. File SE, Zangrossi H, Sanders FL, Mabbutt PS (1994) Raised corticosterone in the rat after exposure to the elevated plus-maze. Psychopharmacology 113:543–546Google Scholar
  7. Fulford AJ, Butler S, Heal DJ, Kendall DA, Marsden CA (1994) Evidence for altered a2-adrenoceptor function following isolation-rearing in the rat. Psychopharmacology 116:183–190Google Scholar
  8. 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 27:183–186Google Scholar
  9. 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 33:457–465Google Scholar
  10. 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 45:363–366Google Scholar
  11. Greenough WT, Madden TC, Fleischmann TB (1972) Effect of isolation, daily handling and enriched rearing on maze learning. Psychon Sci 27:279–280Google Scholar
  12. Holson RR, Scallet AC, Ali SF, Turner BB (1991) “Isolation stress” revisited: isolation-rearing effects depend on animal care methods. Physiol Behav 49:1107–1118Google Scholar
  13. Jones GH, Marsden CA, Robbins TW (1989) Isolation-rearing retards the acquisition opf schedule-induced polydipsia in rats. Physiol Behav 45:71–78Google Scholar
  14. 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 102:364–372Google Scholar
  15. Juraska JM, Henderson C, Muller J (1984) Differential rearing experience, gender and radial maze performance. Dev Psychobiol 17:209–215Google Scholar
  16. 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 1:181–186Google Scholar
  17. Kennett GA (1992) 5-HT1C receptor antagonists have anxiolytic-like actions in the rat social interaction model. Psychopharmacology 107:379–384Google Scholar
  18. Kennett GA, Curzon G (1988) Evidence thatmCPP may have behavioural effects mediated by central 5-HT1C receptors. Br J Pharmacol 94:137–147Google Scholar
  19. 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 118:178–182Google Scholar
  20. Parker V, Morinan A (1986) The socially-isolated rat as a model for anxiety. Neuropharmacology 25:663–664Google Scholar
  21. 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 262:125–131Google Scholar
  22. 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 84:195–205Google Scholar
  23. 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 111:150PGoogle Scholar
  24. 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 116:56–64Google Scholar
  25. Walsh RN, Cummins RA (1976) The open field test: a critical review. Psychol Bull 83:482–504Google Scholar
  26. Whitton P, Curzon G (1990) Anxiogenic-like effect of infusing 1-(3-chlorophenyl)piperazine (mCPP) into the hippocampus. Psychopharmacology 100:138–140Google Scholar
  27. Wright IK, Ismail H, Upton N, Marsden CA (1991a) Effect of isolation rearing on 5-HT agonist-induced responses in the rat. Psychopharmacology 105:259–263Google Scholar
  28. 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 50:1129–1132Google Scholar
  29. 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 109:338–346Google Scholar

Copyright information

© Springer-Verlag 1996

Authors and Affiliations

  • K. C. F. Fone
    • 1
  • K. Shalders
    • 1
  • Z. D. Fox
    • 1
  • R. Arthur
    • 1
  • C. A. Marsden
    • 1
  1. 1.Department of Physiology and Pharmacology, Queen's Medical CentreNottingham UniversityNottinghamUK

Personalised recommendations