Early cannabinoid exposure influences neuroendocrine and reproductive functions in mice: II. Postnatal effects

Maternal exposure to delta 9-tetrahydrocannabinol (THC), the major psychoactive component in marihuana, or to the non-psychoactive cannabinol (CBN) or cannabidiol (CBD) alters male reproductive functions and brain biogenic amines in male and female offspring. Postnatal exposure to THC or CBN reduced body weights, while testicular weights were lower in CBD-exposed mice. Testicular testosterone (T) levels were also lower in CBN- and CBD-exposed animals. Postnatal cannabinoid exposure reduced plasma luteinizing hormone (LH) levels in intact and castrated adults. Although basal T production in vitro was not affected by postnatal cannabinoid exposure, testes from CBD-exposed males were more responsive to gonadotropin stimulation. In contrast, in vivo responsiveness to intratesticular human chorionic gonadotropin (hCG) administration was significantly reduced in THC- and CBD-exposed males. Pituitary weights and their basal LH production in vitro was higher in THC- or CBN-exposed mice. Pituitaries from cannabinoid-exposed males were less responsive to LH releasing hormone (RH) stimulation, however, hypothalamic LHRH content was significantly higher in the THC-exposed males. Hypothalamic dopamine (DA) levels were significantly lower in CBN-exposed castrated mice, compared to castrated controls. The reduction in hypothalmic norepinephrine (NE) in THC- and CBN-exposed castrates after alpha-methylparatyrosine (alpha-MPT) was significantly less than that observed in control castrates. Hypothalamic DA levels were depleted to a greater extent in CBD-exposed males. Brain levels of serotonin (5-HT) and 5-HIAA were significantly higher in castrated, than in intact THC-exposed males. In ovariectomized CBN-exposed females, hypothalamic NE levels were lower, while the alpha-MPT-induced depletion of NE was less in CBD-exposed, compared to control females. Levels of 5-HT were lower only in THC-exposed females. Plasma levels of LH were significantly higher in CBN-exposed, while plasma levels of FSH were reduced in THC- and CBD females. Maternal exposure to psychoactive or non-psychoactive cannabinoids on the day of parturition results in long term alterations in neuroendocrine function in male and female offspring. It is possible that the observed alterations in biogenic amines may mediate the effects of cannabinoids on pituitary and gonadal function.