Delta-9-tetrahydrocannabinol attenuates luteinizing hormone release induced by electrochemical stimulation of the medial preoptic area.
Despite diverse pharmacological actions, drugs commonly used for blocking ovulation in the rat have not been observed to exert differential effects on the LH response to preoptic stimulation, thus suggesting blocking action above the final hypothalamic GnRH pathway. To determine if ovulatory blockade by delta-9-tetrahydrocannabinol (THC) is consistent with that scheme, LH surges evoked by preoptic stimulation were contrasted with those elicited during blockade by atropine (ATR), a classic ovulation-blocking agent with which other drugs have been compared. THC (10 mg/kg) or ATR (350 mg/kg) treatment before the proestrous critical period uniformly blocked LH release and ovulation in sham-stimulated rats. Preoptic stimulation evoked LH surges after both drug treatments (p less than 0.001), peak levels increasing with the intensity of stimulation (p less than 0.05). However, both maximum LH concentration (p less than 0.05) and total integrated LH release (p less than 0.01) were lower in THC-blocked rats. Inspection of the oviducts revealed no difference in the incidence of ovulation or the number of ova discharged. The reduced LH response during THC blockade was not attributable to variation in the extent or locus of histologically determined stimulation sites. These results distinguish THC from ATR and, by extension, other blocking drugs that do not overtly affect the LH response to preoptic stimulation. Thus, ovulatory blockade by THC may involve a different mechanism, which likely includes inhibitory action within the preoptic-to-tuberal GnRH pathway.
Tyrey
L
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Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, North Carolina 27710.
D000818:Animals; D001285:Atropine; D013759:Dronabinol / Q000494:pharmacology*; D004558:Electric Stimulation; D005260:Female; D007986:Luteinizing Hormone / Q000097:blood*; D011301:Preoptic Area / Q000378:metabolism / Q000502:physiology*; D011863:Radioimmunoassay; D051381:Rats; D013223:Statistics as Topic; D013268:Stimulation, Chemical
D001285:Atropine; D013759:Dronabinol; D007986:Luteinizing Hormone