The effects of delta-9-tetrahydrocannabinol administration in the regulation of female rat sociosexual behaviour

Abstract

Cannabis has been legalized in several countries either for recreational or medicinal purposes. By targeting the endocannabinoid system, their main psychoactive compound delta-9-tetrahydrocannabinol (THC), modulates female motivated behaviours, which are influenced by the presence of sex hormones. Both medial preoptic nucleus (MPN) and ventromedial nucleus of the hypothalamus (VMN) are involved in the modulation of female sexual responses, as the first triggers proceptivity and the latter triggers receptivity. These nuclei are modulated by glutamate, that inhibits female receptivity, and GABA, that has a dichotomous action in female sexual motivation. Here, we evaluated the action of THC on the modulation of social and sexual behaviours, on signalling pathways of MPN and VMN and how sex hormones influence these parameters. Behavioural testing was conducted in young ovariectomized female rats, given sex hormones (oestradiol benzoate, EB, and progesterone, P) and THC. After the testing, the animals were sacrificed and the brains processed for vesicular glutamate transporter 2 (VGlut2) and GAD (glutamic acid decarboxylase) 65/67 immunofluorescence. The behavioural results showed that females given EB+P exhibited a higher preference for the male partner, a higher proceptivity and receptivity than control or females given only EB, suggesting that the presence of both hormones facilitates females' sexual response, and EB alone inhibits female sexual behaviour. In all measured parameters, females treated with THC presented similar or even more facilitated behavioural responses than the ones that didn't receive THC. Immunofluorescence results in the MPN exhibited a decreased expression of GAD in THC-treated rats and an increased expression of VGlut2 in EB-treated rats. In the VMNvl it was shown that THC decreased GAD and increased VGlut2 expression, which suggest a more facilitated receptive and behavioural response. To conclude, the present data suggest that THC induces a male preference and increases sexual behaviour by reducing the inhibitory action of MPN over VMN and by directly increasing excitation and diminishing inhibition of the VMNvl.