Failure of adrenergic and cholinergic blocking agents to block ovulation in the rat

Abstract

Mature Sprague-Dawley rats were used in a study of the mode of action of Dibenamine (30 mg/kg), Dibenzyline (10 mg/kg), and Pathilon (35 mg/kg) blockade of spontaneous ovulation-inducing hormone (LH) release. All three agents effectively blocked the release of LH if administered subcutaneously prior to the "critical period" on the day of proestrus (1:00 pm), but each failed to block the release of LH if administered at 5:00 pm on the day of proestrus. When each drug was administered daily at 5:00 pm, vaginal cycles were interrupted but returned to normal after 12–16 days' treatment. After such chronic treatment the animals were then treated with the drug at either 1:00 pm or 5:00 pm on the day of proestrus. A minimum of 80% of the animals released LH and ovulated normally in all six groups. Studies using adrenal ascorbic acid depletion indicate that the animals "adapt" to each drug within 9 days' treatment, and each drug retains its specific blocking properties. The results indicate that the drugs prevent LH release indirectly and not through their respective blocking properties. The findings suggest a reciprocal relationship between the release of LH in amounts which induce ovulation and the release of adrenocorticotrophic hormone (ACTH) following adequate stimulation.