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

Abstract

Rationale: Previous experiments have shown that the disruptive effect of central 5-HT depletion on interval timing behaviour is critically dependent upon 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 receptors affects timing.

Objective: To examine the effects of the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) on performance 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 procedure) and a discrete-trials schedule in which rats were trained to discriminate the durations of light stimuli (interval bisection task).

Methods: In experiment 1, rats were trained under the free-operant psychophysical procedure to respond on two levers (A and B) in 50-s trials in which reinforcement 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 between levers was permitted; for another group, it was prevented. In experiment 2, rats were trained to press lever A after a 2-s stimulus and lever B after an 8-s stimulus, and were then tested with stimuli of intermediate durations. 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, quantitative indices of timing were derived from the psychophysical functions (%B responding vs time).

Results: In experiment 1, 8-OH-DPAT (25, 50, 100 and 200 microg 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 Weber fraction in both versions of the task without displacing the curve.

Conclusions: These results show that 8-OH-DPAT disrupts timing behaviour. The results of experiment 1 are consistent with the proposal that 5-HTergic mechanisms 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 involved in timing tasks involving temporal distribution of responding and discrimination of the durations of exteroceptive stimuli.