Cannabinoid receptor antagonism increases female sexual motivation

The current experiments examined whether treatment with a CB1 antagonist/inverse agonist (AM251) affects sexual motivation, proceptivity, and receptivity in female rats. In experiment #1, 92 Long–Evans rats were tested for their socio-sexual motivation via a runway methodology. Motivation to approach and maintain close proximity to an empty goalbox, a female, and a male target was assessed following hormonal and drug treatment. Hormone treatments were: oil vehicle, 10 μg estradiol, and 10 μg estradiol + 500 μg progesterone. Drug doses were 0, 2, and 4 mg/kg AM251 (IP, 60 min prior to testing). In experiment #2, 32 female subjects were tested for receptivity and proceptivity in a paced mating chamber. Subjects were given either a high (10 μg estradiol + 500 μg progesterone) or low dose of hormones (2 μg estradiol + 250 μg progesterone), and either vehicle or 2 mg/kg AM251. AM251 significantly increased sexual motivation for a male target in the runway in females primed with both estradiol and progesterone. AM251 also enhanced lordosis (in low hormone females) and increased hop-darts. These findings suggest that endocannabinoids tonically inhibit estrous behaviors. Cannabinoid antagonists could serve as new treatment option for women suffering from abnormally low libido.