Endocannabinoid modulation of male rat sexual behavior

Psychopharmacology (Berl). 2008 Jul;198(4):479-86. doi: 10.1007/s00213-007-0901-1. Epub 2007 Aug 13.


Rationale: 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.

Materials and 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amidohydrolases / antagonists & inhibitors
  • Animals
  • Appetitive Behavior / drug effects
  • Arachidonic Acids / antagonists & inhibitors
  • Arachidonic Acids / pharmacology
  • Benzamides / pharmacology
  • Cannabinoid Receptor Modulators / agonists
  • Cannabinoid Receptor Modulators / antagonists & inhibitors
  • Cannabinoid Receptor Modulators / physiology*
  • Carbamates / pharmacology
  • Consummatory Behavior / drug effects
  • Dose-Response Relationship, Drug
  • Ejaculation / drug effects
  • Endocannabinoids*
  • Enzyme Inhibitors / pharmacology
  • Male
  • Piperidines / pharmacology
  • Polyunsaturated Alkamides / antagonists & inhibitors
  • Pyrazoles / pharmacology
  • Rats
  • Rats, Long-Evans
  • Receptor, Cannabinoid, CB1 / antagonists & inhibitors
  • Sexual Behavior, Animal / drug effects
  • Sexual Behavior, Animal / physiology*


  • Arachidonic Acids
  • Benzamides
  • Cannabinoid Receptor Modulators
  • Carbamates
  • Endocannabinoids
  • Enzyme Inhibitors
  • Piperidines
  • Polyunsaturated Alkamides
  • Pyrazoles
  • Receptor, Cannabinoid, CB1
  • cyclohexyl carbamic acid 3'-carbamoylbiphenyl-3-yl ester
  • AM 251
  • Amidohydrolases
  • fatty-acid amide hydrolase
  • anandamide
  • N-(4-hydroxyphenyl)arachidonylamide