Differential Time- and Dose-Dependent Effects in the Haloperidol Blockade of Luteinizing Hormone Release and Ovulation

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Abstract
The capacity of haloperidol (Haldol) to block luteinizing hormone (LH) release and ovulation was investigated with particular reference to its effectiveness during the ‘critical period’ on the afternoon of proestrus in normal, cycling female rats. Haldol was injected subcutaneously at 13.30 h in one of five dosage levels (0.125, 0.25, 0.5, 1.0, or 4.0 mg/kg), or at 09.30 h in a single dose of 1.0 mg/kg. Control animals received the corn oil vehicle at 13.30 or 09.30 h. Blood samples were taken by means of intra-atrial catheters which had been implanted on the day prior to Haldol treatment. Oviducts were examined for the presence of ova at 10.00 h on the day following the experiment (estrus). Haldol was found to be ineffective at 13.30 h when given at dosage levels which were shown by previous authors, and in the present experiment, to be capable of blocking LH release and ovulation after injection at 09.30 h. Although LH levels and the numbers of ova released were inversely related to the dose of Haldol administered at 13.30 h, well-defined LH surges were still present and the occurrence of ovulation was not significantly inhibited. Haldol was found to block LH release and ovulation, however, when injected at 13.30 h at the highest dosage level (4.0 mg/kg). The fact that low doses of Haldol blocked in the morning but not in the afternoon indicates that the morning blockade must be mediated by a secondary action of the drug which required a certain period of time to be effective. The blockade by the high dose of Haldol in the afternoon, however, was probably due to a direct action on LH releasing mechanisms.