Anandamide Transforms Noncopulating Rats into Sexually Active Animals


Gabriela Rodríguez-Manzo, PhD, Departamento de Farmacobiología, Cinvestav-Sede Sur, Czda. de los Tenorios 235, Col. Granjas Coapa, Mexico City 14330, Mexico. Tel: (5255)50612871; Fax: (5255) 50612863; E-mail:


Introduction.  Noncopulating (NC) male rats are apparently normal and healthy animals that will not mate despite repeated exposure to sexually receptive females. Several lines of evidence suggest the involvement of endogenous opioids in this sexual inhibitory state. Endogenous opioids and endocannabinoids are neuromodulators of neurotransmitter release, although through different mechanisms.

Aim.  To establish if the endocannabinoid anandamide was able to induce sexual behavior expression in male rats classified as noncopulators.

Methods.  NC male rats were intraperitoneally (i.p.) injected with anandamide or vehicle and tested for copulatory behavior with a receptive female during 120 minutes. Fourteen days after anandamide or vehicle injection, the animals were subjected to a second sexual behavior test during 60 minutes.

Main Outcome Measures.  The percentage of rats showing male sexual behavior responses: mount, intromission, ejaculation, and copulation resumption after ejaculation and the specific sexual behavior parameters were quantified.

Results.  Anandamide injection induced sexual behavior expression in 50% of previously NC rats, while the NC animals injected with vehicle did not show sexual behavior. The responding animals executed several successive ejaculatory series and were still capable of showing sexual behavior 14 days after anandamide injection. Copulation in these rats (the first copulatory series) was characterized by a large number of mounts and intromissions preceding ejaculation, as well as by statistically significant increases in the latencies to mount, intromit, and ejaculate when compared with the sexual performance of sexually naïve animals copulating for the first time.

Conclusion.  The endocannabinoid anandamide transforms previously NC rats into sexually active animals, capable of showing sexual behavior in a long-lasting manner. Only half of the NC population responds to anandamide injection, suggesting that different mechanisms underlie the sexual inhibition of NC rats. The endocannabinoid system seems to play a role in the regulation of male rat sexual behavior expression. Canseco-Alba A and Rodríguez-Manzo G. Anandamide transforms noncopulating rats into sexually active animals. J Sex Med 2013;10:686–693.