Acute effect of delta1-tetrahydrocannabinol on the hypothalamo-pituitary-ovarian axis in the rat.

Administration of delta1-tetrahydrocannabinol (delta1-THC), the principal psychoactive ingredient of cannabis, to proestrous rats (2 mg/rat, i.p., between 12.00 and 16.00 h) suppressed the proestrous rise in the plasma levels of LH, FSH and prolactin (Prl) and caused a 24 h delay in ovulation. Furthermore, the increased accumulation of prostaglandins of the E-type (PGE) in the ovaries, normally seen on the evening of proestrus, was prevented. Earlier (08.00-10.30 h) or later (18.00 h) administration of the drug on the day of proestrus was only partially effective in inhibiting ovulation. The suppressive effects of delta1-THC on ovulation and gonadotropin secretion were prevented by administration of gonadetropin releasing hormone (GnRH, 0.2 microgram/rat) 1 h after the drug, indicating that the central action of delta1-THC was exerted on the hypothalamus and not on the pituitary gland. Administration of ovine luteinizing hormore (oLH, 2.5 microgram/rat at 16.30 h on the day of proestrus restored ovulation and ovarian PGE accumulation in Nembutal-treated rats, but not in delta1-THC-treated rats; higher doses of oLH (5-10 microgram/rat) reversed the action of delta1-THC on these two parameters.