Effects of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) on performance on two operant timing schedules

Rationale: Previous experiments have shown that the disruptive effect of ce ntral 5-HT depletion on interval timing behaviour is critically dependent u pon the particular timing schedule used. However, it is not known how acute disruption of 5-HTergic function brought about by drugs acting at 5-HT rec eptors affects timing. Objective: To examine the effects of the 5-HT1A rece ptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) on performa nce on two quantitative timing schedules, a free-operant schedule in which rats were trained to distribute their responses differentially between two levers during the course of a 50-s trial (free-operant psychophysical proce dure) and a discrete-trials schedule in which rats were trained to discrimi nate the durations of light stimuli (interval bisection task). Methods: In experiment 1, rats were trained under the free-operant psychophysical proce dure to respond on two levers (A and B) in 50-s trials in which reinforceme nt was provided intermittently for responding on A in the first half, and B in the second half, of the trial. For one group, repetitive switching betw een levers was permitted; for another group, it was prevented. In experimen t 2, rats were trained to press lever A after a 2-s stimulus and lever B af ter an 8-s stimulus, and were then tested with stimuli of intermediate dura tions. For one group, a 'poke response' (depression of a central tray flap) was required after stimulus presentation to effect lever presentation; for the other group this requirement did not operate. In both experiments, qua ntitative indices of timing were derived from the psychophysical functions (%B responding vs time). Results: In experiment 1, 8-OH-DPAT (25, 50, 100 a nd 200 mu g kg(-1) s.c.) displaced the psychophysical curve to the left in both versions of the schedule. In experiment 2, 8-OH-DPAT increased the Web er fraction in both versions of the task without displacing the curve. Conc lusions: These results show that 8-OH-DPAT disrupts timing behaviour. The r esults of experiment 1 are consistent with the proposal that 5-HTergic mech anisms help to regulate the period of the hypothetical pacemaker. However, the results of experiment 2 do not support this suggestion. Taken together, the results support the notion that different neural mechanisms may be inv olved in timing tasks involving temporal distribution of responding and dis crimination of the durations of exteroceptive stimuli.