Effect of 8-OH-DPAT on temporal discrimination following central 5-hydroxytryptamine depletion

The 5-hydroxytryptamine (5-HT)(1A) receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) alters performance in discrete-trials timing schedules. 5-HT1A receptors occur both presynaptically and postsynaptically, but it is not known which receptor population mediates the effects of 8-OH-DPAT on timing, Rats received intra-raphe injections of 5,7-dihydroxytryptamine (n = 16) or sham lesions (n = 14). They were trained in a discrete-trials psychophysical procedure in which levers were presented at a predetermined time after the onset of each trial (2.5, 7.5,.., 47.5 s). A response on lever A was reinforced if lever presentation occurred < 25 s after trial onset; a response on lever B was reinforced if lever presentation occurred > 25 s after trial onset. After 70 preliminary sessions, the rats received 8-OH-DPAT (25, 50, 100, 200 mug kg(-1) sc) and saline vehicle, The percentage of responses on lever B (%B) increased as a function of time from trial onset. Under the baseline (vehicle-treatment) condition, performance did not differ between the two groups. 8-OH-DPAT did not alter the indifference point (time corresponding to %B = 50%), but dose-dependently increased the Weber fraction in both groups. Forebrain concentrations of 5-HT and 5-HIAA in the lesioned group were approximately 10% of control levels. The results suggest that the effect of 8-OH-DPAT on performance on discrete-trials timing schedules is mediated by postsynaptic 5-HT1A receptors. (C) 2002 Elsevier Science Inc. All rights reserved.