Endocannabinoid modulation of male rat sexual behavior.
BACKGROUND
Synthetic and plant-derived cannabinoid CB(1) receptor agonists have consistently been shown to impair sexual behavior in male rodents; however, the role of the endocannabinoid system in regulating copulatory processes is largely unknown. The aim of this experiment was to determine the effect of pharmacological facilitation or antagonism of endocannabinoid signaling on male rat sexual behavior.


METHODS
Male Long-Evans rats were administered a single injection of either the cannabinoid CB(1) receptor antagonist AM251 (1, 2, or 5 mg/kg), the fatty acid amide hydrolase (FAAH) inhibitor URB597 (0.1, 0.3, or 0.5 mg/kg), or the anandamide uptake inhibitor/FAAH inhibitor AM404 (1, 2, and 5 mg/kg), or their respective vehicles, and examined on parameters of appetitive and consummatory sexual behavior.


RESULTS
Inhibition of anandamide metabolism through URB597 had no effect on any parameter of sexual behavior. However, the highest dose of AM404 increased the latency to engage in intromitting behavior, but had no other effect on sexual behavior, suggesting that this effect may be due to the sedative-suppressive effects of this drug. AM251 produced a dose-dependent facilitation of ejaculation, such that the number of intromissions required to achieve ejaculation and the ejaculation latency were reduced by AM251 administration.


CONCLUSIONS
These data suggest that antagonism of the CB(1) receptor facilitates ejaculatory processes, an effect which may be due to interactions with neuropeptidergic systems in the hypothalamus, and further, suggest a novel target for pharmacological agents aimed at treating ejaculatory-based sexual dysfunction.
Gorzalka
Boris B
BB
Department of Psychology, University of British Columbia, Vancouver, BC, Canada, V6T1Z4. bgorzalka@psych.ubc.ca
Morrish
Anna C
AC
Hill
Matthew N
MN
D000581:Amidohydrolases / Q000037:antagonists & inhibitors; D000818:Animals; D001070:Appetitive Behavior / Q000187:drug effects; D001095:Arachidonic Acids / Q000037:antagonists & inhibitors / Q000494:pharmacology; D001549:Benzamides / Q000494:pharmacology; D063385:Cannabinoid Receptor Modulators / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D002219:Carbamates / Q000494:pharmacology; D003259:Consummatory Behavior / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004542:Ejaculation / Q000187:drug effects; D063388:Endocannabinoids; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008297:Male; D010880:Piperidines / Q000494:pharmacology; D053284:Polyunsaturated Alkamides / Q000037:antagonists & inhibitors; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D020318:Rats, Long-Evans; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors; D012726:Sexual Behavior, Animal / Q000187:drug effects / Q000502:physiology*; D000099252:Fatty Acid Amide Hydrolases
D000581:Amidohydrolases; D001095:Arachidonic Acids; D001549:Benzamides; D063385:Cannabinoid Receptor Modulators; D002219:Carbamates; D063388:Endocannabinoids; D004791:Enzyme Inhibitors; D010880:Piperidines; D053284:Polyunsaturated Alkamides; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D000099252:Fatty Acid Amide Hydrolases; C500528:cyclohexyl carbamic acid 3'-carbamoylbiphenyl-3-yl ester; C103505:AM 251; C078814:anandamide; C107594:N-(4-hydroxyphenyl)arachidonylamide
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