Dopamine receptors involved in prolactin secretion pharmacologically characterized by means of 3-PPP enantiomers

Abstract

3-(3-Hydroxyphenyl)-N-n-propylpiperidine (3-PPP) is a novel compound existing in two enantiomers which, as judged by recent biochemical and behavioural studies, both have clearcut though differential effects on central dopamine (DA) receptors. Thus, while both enantiomers act in low doses as agonists preferentially on autoreceptors, in higher doses the (+)-form is an agonist also postsynaptically while the (-)-form acts as an antagonist on postsynaptic DA receptors in the striatum and in the limbic system. In the present study both enantiomers were evaluated with respect to their effects on pituitary DA receptors involved in prolactin release. In previously untreated rats, no increase in prolactin release was observed after administration of either enantiomer in low or high doses. The lack of effect of high doses of the (-)-form indicates that DA receptors on the loctotrophs are pharmacologically different from postsynaptic DA receptors in nigrostriatal a mesolimbic systems. The finding that both enantiomers exerted a dose-dependent prolactin suppressive effect in reserpine-pretreated animals suggests instead that DA receptors on the lactotrophs are pharmacologically similar to DA autoreceptors in the brain. The effect of both 3-PPP enantiomers on prolactin release in reserpine-pretreated animals was antagonized by haloperidol, sulpiride and metaclopramide while pimozide and clozapine appeared less active. This finding is discusse with respect to possible selectivity on pre- vs. postsynaptic DA receptors for various antagonists.