[Abstract Title]. - Society for Neuroscience

Program#/Poster#: 291.9/RR84
Topic: F.02.j. Learning and memory: Pharmacology
Title: Phencyclidine-induced reversal learning deficits in rats; role of 5-HT2C and 5-HT1A
receptors
Authors: *S. L. MCLEAN 1 , M. L. WOOLLEY 2 , J. C. NEILL 1 ;
1 Sch. of Pharm., Univ. Bradford, Bradford, United Kingdom; 2 GlaxoSmithKline, Harlow, United
Kingdom
Abstract: Introduction: Phencyclidine (PCP) produces robust deficits in models of relevance to
cognition in schizophrenia including reversal learning, novel object recognition, and attentional
set-shifting in our laboratory in the rat. There is evidence for involvement of 5-HT receptor
mechanisms, specifically 5-HT1A and 5-HT2C receptors in improving cognition in schizophrenia.
Aim: To investigate the involvement of 5-HT receptor mechanisms in sub-chronic PCP induced
reversal learning deficits in female rats.
Methods: Adult female hooded-Lister rats were trained to perform an operant reversal learning
task. Rats received sub-chronic PCP (2 mg/kg) or vehicle (1 ml/kg) i.p. twice daily for seven
days, followed by 7-days washout. In experiment 1, PCP-treated rats received the selective 5-
HT2C receptor antagonist, SB-243213A (1.0, 3.0, 10.0; i.p.) or vehicle and were tested 30
minutes later. In experiment 2, PCP-treated rats received buspirone (0.15625, 0.3125, 0.625
mg/kg, i.p.) in combination with the 5-HT1A antagonist WAY100635 0.3mg/kg or vehicle 30
min prior to buspirone and were tested 30 minutes later.
Results: Data are expressed as mean ± SEM and analysed by ANOVA followed by post-hoc
Dunnett‟s t-test. In all experiments sub-chronic PCP significantly impaired reversal phase
performance (p