5-HT2C receptor mediation of unconditioned escape behaviour in the unstable elevated exposed plus maze.
OBJECTIVE
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-HT2C receptor. This study aimed to examine the involvement of the 5-HT2C receptor in the unconditioned fear responses observed in the UEEPM (after an acute dose of mCPP) by pre-treatment with the selective 5-HT2C 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-HT2C receptor subtype.
Jones
Nicholas
N
Department of Psychology, University College London, Gower Street, London WC1E 6BT, UK. nick@psychol.ucl.ac.uk
Duxon
Mark S
MS
King
Sheila M
SM
D000631:Aminopyridines / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004924:Escape Reaction / Q000187:drug effects* / Q000502:physiology; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology; D005239:Fear / Q000187:drug effects* / Q000502:physiology; D007211:Indoles / Q000494:pharmacology; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D010879:Piperazines / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D044405:Receptor, Serotonin, 5-HT2C; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D013997:Time Factors
C107820:6-chloro-5-methyl-1-((2-(2-methylpyrid-3-yloxy)pyrid-5-yl)carbamoyl)indoline; D000631:Aminopyridines; D007211:Indoles; D010879:Piperazines; D044405:Receptor, Serotonin, 5-HT2C; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; C015068:1-(3-chlorophenyl)piperazine