Affinity for the dopamine D2 receptor predicts neuroleptic potency in decreasing the speed of an internal clock.

For each of five neuroleptics (chlorpromazine, haloperidol, pimozide, promazine, and spiroperidol), the dose required to produce a rightward horizontal shift of 15-20% for psychophysical bisection functions that relate the percentage of long responses to signal duration was determined in rats for two different signal ranges (2-8 sec and 4-16 sec). Affinity for the dopamine D2 receptor (from in vitro studies) predicted neuroleptic potency in producing the criterion shift of the timing functions, whereas affinity for other aminergic receptors (D1, D3, the alpha-noradrenergic receptor, S1, and S2) did not. The conclusion is that dopamine D2 receptors play a major role in determining the rate of temporal integration for time estimation.