Pharmacological studies of performance on the free-operant psychophysical procedure

In the free-operant psychophysical procedure (FOPP), reinforcement is provided intermittently for responding on lever A in the first half and lever B in the second half of a trial. Temporal differentiation is measured from the psychometric function (percent responding on B, %B, versus time from trial onset, t), the index of timing being T50, the value of t at %B = 50. T50 is reduced by acute treatment with 5-hydroxytryptamine (5-HT1A, 5-HT2A) and dopamine (D1-like, D2-like) receptor agonists. The effects of the agonists can be reversed by the respective antagonists of these receptors. Evidence is reviewed suggesting that the effect of endogenous 5-HT is mediated by 5-HT2A receptors and the effect of endogenous dopamine by D1-like receptors. Data are presented on the effects of lesions of the prefrontal cortex and corpus striatum on the sensitivity of performance on the FOPP to D1-like and D2-like receptor agonists. Lesions of the nucleus accumbens, but not the dorsal striatum or prefrontal cortex, attenuated the effects of a D1-like receptor agonist, 6-chloro-2,3,4,5-tetrahydro-1-phenyl-1H-3-benzazepine [SKF-81297], but not a D2-like receptor agonist, quinpirole, on T50. The results indicate that a population of D1-like receptors in the ventral striatum may contribute to the control of timing performance on the FOPP.This article is part of a Special Issue entitled: SQAB 2012.

► The authors’ research on timing in the free-operant psychophysical procedure (FOPP) is reviewed. ► 5-Hydroxytryptamine (5-HT1A, 5-HT2A) and dopamine (D1-like, D2-like) agonists disrupt timing. ► Effects of endogenous 5-HT may be mediated by 5-HT2A and endogenous dopamine by D1-like receptors. ► New data are presented on the effects of prefrontal cortical and striatal lesions. ► Ventral striatal lesions abolished the effects of a D1-like receptor agonist on timing in the FOPP.