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

Acute treatment with Delta(9)-tetrahydrocannabinol [Delta(9)-THC; 0.5 or 1. 0 mg/kg b.w. intravenously (i.v.)], the major psychoactive constituent of m arijuana, produces a dose-related suppression of pulsatile luteinizing horm one (LPI) secretion in ovariectomized rats. To determine whether Delta(9)-T HC produces this response by altering neurotransmitter and/or neuropeptide systems involved in the regulation of LH secretion, ovariectomized rats wer e preheated with antagonists for dopamine, norepinephrine, serotonin, or op ioid receptors, and the effect of Delta(9)-THC on LN 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 o pioid receptor antagonists naloxone (1-4 mg/kg, i.v.) or naltrexone (7 mg/k g, i.v.), the noradrenergic alpha(2)-receptor antagonist idazoxan (10 mu g/ kg, i.v.), or the serotonin 5-HT1C/2 receptor antagonist ritanserin (1 or 5 mg/kg b.w., i.p.), did not alter Delta(9)-THC-induced inhibition of pulsat ile LH secretion. Pretreatment with a relatively high dose of the beta-adre nergic receptor blocker propranolol (6 mg/kg, i.v.) attenuated the ability of the low THC dose to inhibit LH release; however, lower doses of proprano lol were without effect. Furthermore, the ability of a relatively nonspecif ic serotonin 5-HT1A/1B receptor antagonist pindolol (4 mg/kg,s.c.) or the s pecific 5-HT1A receptor antagonist WAY-100635 (1 mg/kg, s.c.) to significan tly attenuate THC-induced LH suppression indicates that activation of serot onergic 5-HT1A receptors may be an important mode by which THC causes inhib ition of LH release in the ovariectomized rat. (C) 1999 Elsevier Science In c. All rights reserved.