Effects of Quipazine and M-Chlorophnylbiguanide (m-CPBG) on the Discrimination of Durations: Evidence for the Involvement of 5-HT2A but Not 5-HT3 Receptors

Rationale: the ability of rats to discriminate durations of extroceptive stimuli is disrupted by 5-ht1a receptor agonists; it is not known whether temporal discrimination is sensitive to stimulation of other 5-ht receptor subtypes. objective: to examine the effect of quipazine, a 5-ht receptor agonist with nanomolar affinity for 5-ht3 receptors and micromolar affinity for 5-ht2a receptors, and m-chlorophenylebiguanide (m-cpbg) on temporal discrimination. methods: twenty-four rats were trained to press the levers for sucrose reinforcement under a discrete trials psychophysical procedure. in each 50-second trial, a light was presented for t second following which two levers (a and b) were presented. a response on a was reinforced if t<25s, and a response on b was reinforced if t> 25s. logistic psychometric functions were fitted to the data, and timing parameters estimated (t50: value oft corresponding to %b= 50; weber fraction: [t75-t25]/2t50, where t75 and t 25 are values of t corresponding to %b= 75 and %b= 25). results: quipazine (0.5-2mg/kg) displaced the psychometric curve to the right and reduced its slope, reflected in increases in t50 and weber fracrtion; m-cpbg (2.5-10 mg/kg) had no effect. the effects of quipazine were reversed by 5-ht2a receptor agonist ketanserin (2mg/kg) but not by 5-ht3 receptor antagonist topanyl 3, 5- dichlorobenzoate (mdl 72222) (1 mg/kg). conclusions: the results indicate that 5-ht2a but not 5-ht3 stimulation disrupts temporal discrimination. the increase in the weber fraction produced by quipazine indicates an impairment of the precision with which the rats discriminated the durations of the light stimulus. the lack of effect of m-cpbg stands in contrast to the robust effect of quipazine. this effect was not altered by co-administration of mdl72222, but was completely abolished by co-administration of ketanserin, which has a very high affinity for 5-ht2 receptors. also these results suggest that 5-ht3 receptor stimulation does not influence temporal discrimination.