A comparative study of the locomotor activity effects of apomorphine and the "atypical dopamine agonists" (piribedil and S3608)

Abstract

Apomorphine and the "atypical dopamine agonists" (piribedil and S3608) dose dependently increase locomotor activity (LA) in rats. The LA effects of all 3 drugs are readily attenuated by pretreatment with pimozide or sulpiride. Reserpine pretreatment or bilateral 6-hydroxydopamine lesions of the nucleus accumbens (NAS) potentiates apomorphine-induced LA but attenuates piribedil- and S3608-induced LA. The latter suggests an indirect mode of action for piribedil and for S3608. However, piribedil and S3608 at concentrations up to 10(-4)M do not cause release or inhibition of 3H-dopamine uptake in synaptosomes prepared from the rat NAS. Sulpiride antagonism of apomorphine-induced LA is surmountable by increasing the dose of apomorphine. Antagonism of piribedil- or S3608-induced LA by sulpiride is not surmountable by increasing the dose of either of the "atypical dopamine agonists". Furthermore, pretreatment with either piribedil or S3608 substantially increases the peak LA inducible by apomorphine. The effects of simultaneous injections of piribedil and S3608 are, however, not additive. These findings suggest that the LA stimulant effects of piribedil and S3608 are mediated via receptors or systems which differ from the receptors involved in the mediation of apomorphine-induced LA.