Synthetic and plant-derived cannabinoid CB1 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.
Materials and methods
Male Long-Evans rats were administered a single injection of either the cannabinoid CB1 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.
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.
These data suggest that antagonism of the CB1 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.
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This research was supported by a Natural Sciences and Engineering Research Council of Canada (NSERC) operating grant to BBG and a Michael Smith Foundation for Health Research postgraduate trainee award and a NSERC Canadian Graduate Scholarship to MNH. The authors would like to thank Shirley Sarkodee-Adoo, Morag Yule, Rajinder Gill, and Eda Karacabeyli for their technical assistance.
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Gorzalka, B.B., Morrish, A.C. & Hill, M.N. Endocannabinoid modulation of male rat sexual behavior. Psychopharmacology 198, 479–486 (2008). https://doi.org/10.1007/s00213-007-0901-1