Inhibition of luteinizing hormone secretion by delta9-tetrahydrocannabinol in the ovariectomized rat: effect of pretreatment with neurotransmitter or neuropeptide receptor antagonists.
Acute treatment with delta9-tetrahydrocannabinol [delta9-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 delta9-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 delta9-THC on LH release was determined. Pretreatment with the D2 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 alpha2-receptor antagonist idazoxan (10 microg/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 delta9-THC-induced inhibition of pulsatile LH secretion. Pretreatment with a relatively high dose of the beta-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-HT1A receptor antagonist WAY-100635 (1 mg/kg, s.c.) to significantly attenuate THC-induced LH suppression indicates that activation of serotonergic 5-HT1A receptors may be an important mode by which THC causes inhibition of LH release in the ovariectomized rat.
Murphy
L L
LL
Department of Physiology, Southern Illinois University School of Medicine, Carbondale 62901-6512, USA. lmurphy@som.siu.edu
Adrian
B A
BA
Kohli
M
M
D018674:Adrenergic Antagonists / Q000494:pharmacology; D000818:Animals; D018492:Dopamine Antagonists / Q000494:pharmacology; D013759:Dronabinol / Q000494:pharmacology*; D005260:Female; D007986:Luteinizing Hormone / Q000378:metabolism*; D010052:Ovariectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D018013:Receptors, Neuropeptide / Q000037:antagonists & inhibitors*; D017981:Receptors, Neurotransmitter / Q000037:antagonists & inhibitors*; D012702:Serotonin Antagonists / Q000494:pharmacology
D018674:Adrenergic Antagonists; D018492:Dopamine Antagonists; D018013:Receptors, Neuropeptide; D017981:Receptors, Neurotransmitter; D012702:Serotonin Antagonists; D013759:Dronabinol; D007986:Luteinizing Hormone