Anandamide reduces the ejaculatory threshold of sexually sluggish male rats: possible relevance for human lifelong delayed ejaculation disorder.

Abstract

The sexually sluggish (SLG) male rat has been proposed as an animal model for the study of lifelong delayed ejaculation, a sexual dysfunction for which no treatment is available. Low endocannabinoid anandamide (AEA) doses facilitate sexual behavior display in normal sexually active and in noncopulating male rats through the activation of CB1 receptors. To establish whether low AEA doses reduced the ejaculatory threshold of SLG male rats by acting at CB1 receptors. SLG male rats were intraperitoneally injected with different doses of AEA (0.1-3.0 mg/kg), the CB1 receptor antagonist AM251 (0.1-3.0 mg/kg), or their vehicles and tested for copulatory behavior during 60 minutes. Animals receiving AEA effective doses were subjected to a second sexual behavior test, 7 days later under drug-free conditions. To determine the participation of CB1 receptors in AEA-induced actions, SLG rats were pretreated with AM251 prior to AEA. The sexual parameters, intromission latency, number of mounts and intromissions, ejaculation latency, and interintromission interval. All sexual behavior parameters of SLG rats were significantly increased when compared with normal sexually experienced animals. Low AEA doses (0.3 and 1 mg/kg) significantly lowered the ejaculatory threshold of SLG rats, reducing the number of pre-ejaculatory intromissions and ejaculation latency. IL, M number, and locomotor activity were unaffected by AEA. Facilitation of the ejaculatory response of SLG rats disappeared 7 days after AEA injection. AM251 lacked an effect on copulation of SLG rats but blocked the AEA-induced lowering of the ejaculatory threshold. AEA appears to specifically target the ejaculatory threshold of SLG rats through the activation of CB1 receptors. This specificity along with the fact that AEA's effects are exerted acutely and at low doses makes this drug emerge as a promising treatment for the improvement of the ejaculatory response in men with primary delayed ejaculation.