Role of 5-HT receptor mechanisms in sub-chronic PCP-induced reversal learning deficits in the rat

Rationale: 5-HT receptor mechanisms have been suggested to mediate improvements in cognition in schizophrenia. Aim: The aim of this study was to investigate the involvement of 5-HT receptor mechanisms in sub-chronic phencyclidine (PCP)-induced reversal learning deficits in female rats, a task of relevance to schizophrenia. Methods: Adult female hooded Lister rats were trained to perform an operant reversal learning task and then received sub-chronic PCP (2 mg/kg) or vehicle intraperitoneally (i.p.) twice daily for 7 days, followed by 7-day washout. Rats then received an acute dose of the 5-HT7 receptor antagonist SB-269970A (1.0, 3.0, and 10.0 mg/kg, i.p.) or vehicle. In experiment 2, PCP-treated rats received the selective 5-HT 2C receptor antagonist, SB-243213A acutely (1.0, 3.0, and 10.0 mg/kg, i.p.) or vehicle. In experiment 3, PCP-treated rats received the 5-HT 1A receptor partial agonist, buspirone (0.15625, 0.3125, and 0.625 mg/kg, i.p.) in combination with the selective 5-HT1A receptor antagonist WAY-100635 (0.3 and 1.0 mg/kg). Results: In all experiments, sub-chronic PCP significantly impaired reversal phase performance (P