Changes in the sensitivity to apomorphine of dopamine receptors modulating dopamine and acetylcholine release after chronic treatment with bromocriptine or haloperidol

LX Cubeddu, IS Hoffmann, MK James and DM Niedzwiecki

The release of dopamine (DA) and of acetylcholine (ACh) was monitored from rabbit striatal slices labeled with [3H]DA and [14C]choline. Chronic treatment with haloperidol (1 mg/kg b. wt. for 28 days, sacrifice 96 hr after last injection) increased the potency of in vitro apomorphine in inhibiting the release of DA and ACh evoked by electrical stimulation when compared to vehicle-treated rabbits. Potentiation of apomorphine effects was greater on DA than on ACh release. The effects of in vitro haloperidol on DA and ACh release and in antagonizing the inhibitory effects of apomorphine were not modified by chronic treatment with haloperidol. Bromocriptine (1.5 mg/kg b.wt. for 7 days, sacrifice 72 hr after last injection) did not affect the evoked release of DA and of ACh, or the sensitivity to apomorphine. However, 15 mg/kg b.wt. of bromocriptine for 7 days and sacrifice 72 hr after last injection, produced a 60 to 70% reduction in the evoked release of DA and ACh, and markedly antagonized the inhibition of DA and ACh release produced by apomorphine. These results indicate that the DA receptors which modulate the release of DA and of ACh play an important physiological role inasmuch as they develop adaptational changes after prolonged receptor activation or inhibition by DA agonists and antagonists, respectively. These adaptational changes affect the potency of DA agonists on release modulatory receptors without modifying that of DA antagonists. The possibility that bromocriptine has a residual agonistic effect on striatal DA receptors 3 days after the last injection cannot be ruled out.

Volume 226, Issue 3, pp. 680-685, 09/01/1983
Copyright © 1983 by American Society for Pharmacology and Experimental Therapeutics