The effects of prenatally administered endogenous cannabinoid on rat offspring

We reported previously that the main psychoactive component of marihuana, delta9 tetrahydrocannabinol (THC), when injected prenatally, temporarily inhibited the developing hypothalamo-pituitary system in rat offspring. In the present study, we investigated the effects of the recently described endogenous ligand for the central cannabinoid receptor, arachidonyl-ethanolamide (anandamide, ANA), on the postnatal development of the hypothalamo-pituitary axis (HPA) when administered during the third week of gestation. Rat pups were killed every fifth day from delivery to the 20th postnatal day; gonads, pituitary, and rest of body were weighed, and samples were collected for analysis of gonadotropin releasing hormone in the hypothalamus and luteinizing hormone, follicle stimulating hormone, prolactin, and growth hormone in the pituitaries and sera. The effects of ANA and THC were compared. Both ANA and THC caused predominantly inhibitory effects on the measured parameters. The inhibition was most pronounced immediately following delivery, whereas at the end of the investigated period (20th postnatal day) no differences were observed. We conclude that endogenous and exogenous cannabinoids have similar but slightly different effects on the developing HPA and that the action is transitory. We postulate that ANA probably acts via central cannabinoid receptors and/or neuroendocrine receptors to function as a neuromodulator.