Modifications of mesolimbic and nigrostriatal dopaminergic activities after intracerebroventricular administration of prolactin.

Abstract

In the present study we examined the effects of intracerebroventricular (i.c.v.) injections of prolactin (PRL) on the presynaptic activity and post-synaptic sensitivity of mesolimbic and nigrostriatal dopaminergic neurons. In addition, the effects of PRL on in vitro release of dopamine (DA) from perifused striatal fragments were examined. Tyrosine hydroxylase (TH) activity and D2 receptor density in the striatum decreased after i.c.v. PRL administration; this was accompanied by an increase in D2 receptor affinity. These effects occurred after i.c.v. administration of PRL to normoprolactinemic rats, although normally they did not appear after administration to animals with pituitary grafting-induced hyperprolactinemia. Thus, in these animals, i.c.v. PRL failed to decrease TH activity and D1 and D2 receptor densities to a significant extent. In the case of D2 receptors, this was probably due to the fact that pituitary grafting-induced hyperprolactinemia itself was able to reduce the density of this receptor. No changes were observed in DA or L-3, 4-dihydroxyphenylacetic acid (DOPAC) contents after i.c.v. administration of PRL to both normo-and hyperprolactinemic animals. Basal and K(+)-evoked DA release in vitro from perifused striatal fragments of normoprolactinemic rats were not affected by the addition of PRL, whereas this hormone enhanced K(+)-evoked DA release when added to perifused striatal fragments from hyperprolactinemic animals. In the limbic forebrain, i.c.v. administration of PRL to normoprolactinemic animals produced a decrease in DA and DOPAC contents and D1 receptor density. Interestingly, none of these effects appeared when PRL was injected to hyperprolactinemic animals. In summary, our results suggest a possible inhibitory role of PRL on the activity of both the nigrostriatal and mesolimbic dopaminergic neuronal systems. These inhibitory effects were reflected in the decreases elicited in a set of neurochemical parameters, indicating either presynaptic activity or postsynaptic sensitivity, after i.c.v.-administered PRL. This observation supports the hypothesis of a possible neuromodulatory role for an extrapituitary PRL on the activity of these neurons, although the fact that most of these effects did not appear when i.c.v. administration was performed in hyperprolactinemic rats also suggests that they are influenced by peripheral PRL levels.