Acute Effect of ▵1–Tetrahydrocannabinol on the Hypothalamo-Pituitary-Ovarian Axis in the Rat

Abstract

Administration of .DELTA.1-tetrahydrocannabinol (.DELTA.1-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 [luteinizing hormone], FSH [follicle stimulating hormone] and prolactin (Prl) and caused a 24 h delay in ovulation. 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) drug administration on the day of proestrus was only partially effective in inhibiting ovulation. Suppressive effects of .DELTA.1-THC on ovulation and gonadotropin secretion were prevented by administration of gonadotropin releasing hormone (GnRH, 0.2 .mu.g/rat) 1 h afer the drug, indicating that central action of .DELTA.1-THC was exerted on the hypothalamus and not on the pituitary gland. Administration of ovine luteinizing hormone (oLH, 2.5 .mu.g/rat) at 16:30 h on the day of proestrus restored ovulation and ovarian PGE accumulation in nembutal-treated rats but not in .DELTA.1-THC-treated rats; higher doses of oLH (5-10 .mu.g/rat) reversed .DELTA.1-THC action on these 2 parameters.