Inhibition of luteinizing hormone secretion by Δ 9-tetrahydrocannabinol in the ovariectomized rat: Effect of pretreatment with neurotransmitter or neuropeptide receptor antagonists

Abstract

Acute treatment with Δ 9-tetrahydrocannabinol [Δ 9-THC; 0.5 or 1.0 mg/kg b.w. intravenously (i.v.)], the major psychoactive constituent of marijuana, produces a dose-related suppression of pulsatile luteinizing hormone (LH) secretion in ovariectomized rats. To determine whether Δ 9-THC produces this response by altering neurotransmitter and/or neuropeptide systems involved in the regulation of LH secretion, ovariectomized rats were pretreated with antagonists for dopamine, norepinephrine, serotonin, or opioid receptors, and the effect of Δ 9-THC on LH release was determined. Pretreatment with the D 2 receptor antagonists butaclamol (1.0 mg/kg b.w., intraperitoneally) or pimozide [0.63 mg/kg, subcutaneously (s.c.)], the opioid receptor antagonists naloxone (1-4 mg/kg, i.v.) or naltrexone (2 mg/kg, i.v.), the noradrenergic α 2-receptor antagonist idazoxan (10 μg/kg, i.v.), or the serotonin 5-HT 1C/2 receptor antagonist ritanserin (1 or 5 mg/kg b.w., i.p.), did not alter Δ 9-THC-induced inhibition of pulsatile LH secretion. Pretreatment with a relatively high dose of the β-adrenergic receptor blocker propranolol (6 mg/kg, i.v.) attenuated the ability of the low THC dose to inhibit LH release; however, lower doses of propranolol were without effect. Furthermore, the ability of a relatively nonspecific serotonin 5-HT 1A/1B receptor antagonist pindolol (4 mg/kg, s.c.) or the specific 5-HT 1A receptor antagonist WAY-100635 (1 mg/kg, s.c.) to significantly attenuate THC-induced LH suppression indicates that activation of serotonergic 5-HT 1A receptors may be an important mode by which THC causes inhibition of LH release in the ovariectomized rat.