Nicholas Jones +44-20-76795377 +44-20-74364276 email@example.com Mark S. Duxon Sheila M. King Department of Psychology, University College London, Gower Street, London WC1E 6BT, UK Neurology CEDD, GlaxoSmithKline, New Frontiers Science Park, Third Avenue, Harlow, Essex CM19 5AW, UK Abstract Rationale and objectives. m-Chlorophenylpiperazine (mCPP) induces panic in humans and dose dependently increases unconditioned escape behaviour in a novel pre-clinical model of extreme anxiety in rats, the unstable elevated exposed plus maze (UEEPM). Numerous studies indicate that the anxiogenic effects of mCPP may be mediated by its action at the 5-HT 2C receptor. This study aimed to examine the involvement of the 5-HT 2C receptor in the unconditioned fear responses observed in the UEEPM (after an acute dose of mCPP) by pre-treatment with the selective 5-HT 2C receptor antagonist SB-242084. Methods. Male Hooded Lister rats received a single dose of SB-242084 (0.1–1.0 mg/kg IP) or vehicle 40 min pre-test followed by a single dose of mCPP (1.0 mg/kg IP) or saline 30 min before being exposed to the UEEPM for a period of 5 min. Subjects' behaviour was analysed to determine the effects of SB-242084 on mCPP-induced increases in escape behaviour. Results. mCPP alone increased animals' propensity to escape from the UEEPM despite producing marked decreases in locomotor/exploratory behaviour. SB-242084 dose dependently inhibited the increases in escape and hypolocomotor effects induced by mCPP. Conclusions. These results suggest that the escape-related behaviours exhibited by animals in the UEEPM are mediated, at least in part, by activation of the 5-HT 2C receptor subtype.
Psychopharmacology – Springer Journals
Published: Nov 1, 2002
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