Effects of quipazine and m-chlorophenylbiguanide (m-CPBG) on the discrimination of durations: evidence for the involvement of 5-HT2A but not 5-HT3 receptors

Abstract

The ability of rats to discriminate durations of exteroceptive stimuli is disrupted by 5-HT(1A) receptor agonists; it is not known whether temporal discrimination is sensitive to stimulation of other 5-HT receptor subtypes. We examined the effect of quipazine, a 5-HT receptor agonist with nanomolar affinity for 5-HT(3) receptors and micromolar affinity for 5-HT(2A) receptors, and m-chlorophenylbiguanide (m-CPBG), a selective 5-HT(3) receptor agonist, on temporal discrimination. Twenty-four rats pressed levers for sucrose reinforcement under a discrete-trials psychophysical procedure. In each 50-s trial, a light was presented for t s, following which two levers (A and B) were presented. A response on A was reinforced if t < 25 s, and a response on B if t > 25 s. Logistic psychometric functions were fitted to the data, and timing parameters estimated (T(50): value of t corresponding to %B = 50; Weber fraction: [T(75)-T(25)]/2T(50), where T(75) and T(25) are values of t corresponding to %B = 75 and %B = 25). Quipazine (0.5-2 mg/kg) displaced the psychometric curve to the right and reduced its slope, reflected in increases in T50 and the Weber fraction; m-CPBG (2.5-10 mg/kg) had no effect. The effects of quipazine were reversed by the 5-HT(2A) receptor antagonist ketanserin (2 mg/kg) but not by the 5-HT3 receptor antagonist topanyl 3,5-dichlorobenzoate (MDL-72222) (1 mg/kg). The results indicate that 5-HT(2A) but not 5-HT(3) receptor stimulation disrupts temporal discrimination.