Counteraction of the haloperidol blockade of ovulation by bromocriptine, and the effect of bromocriptine on LH and prolactin secretion.
Previous experiments showed that haloperidol (Haldol) blocked LH release and ovulation when injected on the day of proestrus in the female rat. The present studies were designed to investigate the mechanism of Haldol blockade and the possibility that bromocriptine (CB) might counteract the effect. One hour prior to subcutaneous injection of an effective dose of Haldol (0.25 mg/kg at 09.30 h), CB was injected intraperitoneally at one of four doses (2.5, 5.0, 7.5, or 10.0 mg/kg at 08.30 h). Bromocriptine was effective at restoring LH release and ovulation, and the optimal dose for this particular experiment was found to be 7.5 mg/kg. The highest dose (10.0 mg/kg), however, resulted in no significant increase in ovulation. Treating animals with CB (5.0, 10.0, or 20.0 mg/kg at 08.30 h) followed by control vehicle showed that high doses of CB caused a significant inhibition of LH release and ovulation. After 20.0 mg/kg there was no significant surge of LH, and although ovulation did occur it was significantly suppressed when compared to control animals (p = 0.017). These results showed that appropriate doses of CB counteract the Haldol blockade of LH release and ovulation. The suppression of Haldol-induced PRL secretion by low-dose CB, without the significant restoration of ovulation, supported the hypothesis that the Haldol blockade was mediated via a direct effect of Haldol on central nervous system control mechanisms. While CB alone exerted a profound inhibition of PRL at low doses, it had no effect on LH release. CB at high doses, however, was inhibitory to both LH release and ovulation.
D000818:Animals; D001971:Bromocriptine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006220:Haloperidol / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D007986:Luteinizing Hormone / Q000097:blood*; D010060:Ovulation / Q000187:drug effects*; D011388:Prolactin / Q000097:blood*; D051381:Rats; D011919:Rats, Inbred Strains
D001971:Bromocriptine; D011388:Prolactin; D007986:Luteinizing Hormone; D006220:Haloperidol