Modulation of reward and aversion processes in the rat diencephalon by neuroleptics: differential effects of clozapine and haloperidol.

The effects of clozapine and haloperidol on self-stimulation in rats were investigated in a shuttle-box that provides concurrent rate-independent indexes of the rewarding and aversive components of intracranial stimulation. The use of two concurrent measures of performance permits the differentiation of specific reward modulation effects from the variety of nonspecific performance decrements that these drugs may produce. Clozapine produced a dose-dependent reduction in reward that could be clearly dissociated from its nonspecific effects. In contrast, the apparent reduction in reward produced by haloperidol could not be dissociated from a nonspecific performance decrement. Consequently, the attenuation of self-stimulation produced by haloperidol does not indicate a direct role for dopamine in modulating reward. It is suggested that the attenuation of reward produced by neuroleptics reflects a reduction in noradrenergic transmission, whereas their nonspecific effects reflect their blockade of dopamine receptors.