Differential effects of some predominantly antiadrenergic and antidopaminergic neuroleptics on the preovulatory surge of FSH, LH and prolactin in rat.

In experiments performed on rats, single subcutaneous doses of predominantly antiadrenergic neuroleptics (thioridazine, propericiazine) significantly depressed the preovulatory serum LH surge. On the contrary, predominantly antidopaminergic drugs (pimozide and in lesser extent thiethylperazine) elevated the circulating LH levels, and reduced pituitary LH content. FSH titers were not altered significantly (excepting by thioridazine). All the neuroleptics increased serum prolactin. The present results, in conjunction with our previous data obtained on the estrous cycle, suggest a stimulatory role of norepinephrine/epinephrine in LH-RH secretion and an inhibitory action of dopamine on the same process. In our experiments only the predominantly antidopaminergic drugs had a pseudopregnancy-inducing effect, which not only elevated PRL levels, but also allowed (rather increased) preovulatory LH surge, and the subsequent development of new corpora lutea. The lack of pseudopregnancy after predominantly antiadrenergic neuroleptics may be attributed mainly to their antiovulatory action preventing the development of fresh corpora lutea.

Effects of amantadine on the estrous cycle in rats.

Amantadine, administered in single doses of 5-25 mg/kg s.c. to normal cycling rats, induced prolonged estrus, i.e. blocking of ovulation. This result supports the inhibitory role of the dopaminergic mechanisms in the LRF secretion. In larger doses, the drug led to persistent diestrus, too, probably by blocking the dopaminergic mechanisms involved in the PIF secretion. The observed effects agree with the partial dopaminergic agonist character of amantadine.

Effects of apomorphine combined with chlorpromazine and pimozide on the estrous cycle in rats.

Chlorpromazine (CPZ) a neuroleptic which has both antiadrenergic and antidopaminergic activity when administered in doses of 5 to 25 mg/kg s.c. inhibited ovulation and induced pseudopregnancy. Pimozide which possesses only an antidopaminergic action induced only pseudopregnancy (in doses between 0.05-10 mg/kg s.c.). Apomorphine (APO), a dopaminergic agonist, prevented the pseudopregnant effect of both neuroleptics, especially of CPZ, but failed to counteract the ovulation-blocking action of CPZ. APO itself had an antiovulatory action, but only in large doses (above 5 mg/kg s.c.), and only in a few animals. Our data plead for the importance of dopaminergic mechanisms in the inhibition of prolactin secretion (by means of PIF) and for the stimulatory role of adrenergic transmission in the ovulation process (by means of LRF). These results fail to support the proposed stimulatory role of dopamine on the LRF secretion. On the contrary, they do not exclude the possibility of its inhibitory action.

The different influence of predominantly antiadrenergic and antidopaminergic neuroleptics on the estrous cycle in rats.

In experiments performed on rats, single subcutaneous doses of predominantly antidopaminergic neuroleptics (fluspirilene, pimozide, and thioproperazine in large doses) elicited persistent diestrus, i.e. pseudopregnancy. Neuroleptics with predominantly antiadrenergic action (levomepromazine, thioridazine, chlorpromazine) as well as phenoxybenzamine injected intraventricularly induced mainly prolonged estrus, i.e. blocking of ovulation. Since pseudopregnancy implies a rise of prolactin secretion, our results indirectly indicate that PIF secretion is stimulated by dopamine. The antiovulatory effect of the antiadrenergic agents, which involves an inhibition of the proestral LH surge, suggests that the discharge of LRF is mediated by an adrenergic mechanism.