Reversible decrease in dopaminergic 3H-agonist binding after 6-hydroxydopamine and irreversible decrease after kainic...

Six days after the unilateral intrastriatal injection of 30 ug 6-hydroxydopamine (6-OHDA) the number of stereospecific 3H-dopamine and 3H-apomorphine binding sites (Bmax) was reduced by 50-60% in the caudate nucleus ipsilateral to the lesion. The dopamine content of the lesioned caudate nucleus was also reduced to 2% of the contralateral side or of sham-operated controls. The preincubation of depleted homogenates with added dopamine reversed the effects of 6-OHDA on the Bmax of 3H-agonists. A similar pattern of depletion, decrease in binding and in vitro reversal by dopamine was observed after a single injection of reserpine (4.0 mg/kg, im.). The intrastriatal injection of kainic acid also lowered the Bmax of 3H-agonists by 65% without altering dopamine content. Preincubation of homogenates of kainic acid-lesioned caudate nuclei with 355 nM (endogenous) dopamine did not reverse the decrease in binding. We conclude that treatments which deplete endogenous dopamine, including the lesion of nigrostriatal terminals, induce a reversible change in the parameters of 3H-agonist binding whereas the destruction of intrinsic caudate neurons with kainic acid results in an irreversible loss of receptors.