Bromocriptine-induced rotation: characterization using a striatal efferent lesion in the mouse

Two lesion techniques were used to elucidate the mode of action of bromocriptine (BRC)-induced behavior in mice. With the first lesion, a unilateral 6-hydroxydopamine (6-OHDA) preparation, BRC administration resulted in contralateral rotation which was blocked by alpha-methyl-para-tyrosine (AMPT), comparable to previous reports using rats. After striatonigral/entopeduncular lesion, mice did not rotate in response to doses of BRC up to 30 mg/kg but did show general activation which was also inhibited by AMPT pretreatment. It is concluded that BRC does not elicit rotation when there is no dopaminergic asymmetry such as that caused by a unilateral 6-OHDA lesion or no asymmetry in the striatonigral or striatoentopeduncular efferents. Since BRC-induced behaviors are dependent on intact presynaptic dopamine and BRC is predominantly a D-2 agonist, behaviors elicited in response to BRC must be the result of coactivation of D-1 receptors by endogenous dopamine. Thus, the behavioral effects of BRC, and perhaps D-2 agonists in general, must be mediated by efferents other than the striatonigral and striatoentopeduncular pathways.