The effects of chronic bromocriptine treatment on behaviour and dopamine receptor binding in the rat striatum

Abstract

Agonist-induced rotation and striatal binding of [ 3H]spiperone ([ 3H]SPIP) were assessed in rats with unilateral lesions of the substantia nigra during and after a period of chronic bromocriptine administration. Agonist-induced rotation significantly increased over a three week period of daily administration of bromocriptine (10 mg/kg i.p.); control animals were tested for agonist-induced rotation at one week intervals, which remained constant. Rotation was increased by chronic bromocriptine administration in response to either of two DA agonists, apomorphine (APO) and bromocriptine, suggesting that increased agonist sensitivity did not reflect a reduction in the metabolism of bromocriptine. Striatal binding of the dopamine D2 radioligand, [ 3H]SPIP, was significantly increased in the denervated striata of nigra-lesioned rats. Chronic bromocriptine administration decreased binding in denervated striata to levels not significantly different from control values. [ 3H]SPIP binding in intact striata was significantly reduced by bromocriptine to below control values. Differences in receptor levels reflected changes in the maximum density of binding sites with no change in affinities. Paradoxical behavioural hypersensitivity developing during chronic bromocriptine levels is not apparently mediated changes in striatal D2 binding sites.