Effects of Delta-9-Tetrahydrocannabinol, Cannabinol and Cannabidiol, Alone and in Combinations, on Luteinizing Hormone and Prolactin Release and on Hypothalamic Neurotransmitters in the Male Rat

Abstract

The acute effects of low oral doses of Δ⁹-tetrahydrocannabinol (THC), cannabinol (CBN) and cannabidiol (CBD) administered alone or in combinations on LH and prolactin (PRL) secretion and on hypothalamic norepinephrine (NE), dopamine (DA) and serotonin (5-HI) dynamics were examined in adult male rats. Plasma LH levels were significantly reduced 60 min after administration of 0.5 mgTHC/kg body weight and 30, 60 and 120 min after administration of THC + CBN or THC + CBD. There were no changes in plasma PRL in response to cannabinoid treatments. The turnover of NE in both the median eminence (ME) and medial basal hypothalamus (MBH) was dramatically affected by all the cannabinoid treatments. Complete suppression of NE turnover occurred 30 min post-THC and 120 min post-THC + CBN in the ME and 120 min post-THC + CBD in the MBH. Cannabinoids did not significantly affect DA turnover in the MBH or the content of NE, DA, 5-HT or 5-hydroxyindole-3-acetic acid in either the ME or MBH. These data demonstrate that treatment of adult male rats with a low dose of THC suppresses LH secretion and that CBN and CBD potentiate this action of THC. Although the mechanisms responsible for the inhibition of LH release by cannabinoids cannot be positively identified from these experiments, the results suggest that alterations in hypothalamic noradrenergic activity may be involved in this effect.

Progesterone receptor and dopamine receptors are required in Δ 9 -tetrahydrocannabinol modulation of sexual receptivity in female rats

“…Interestingly, in addition to dopaminergic neurons, THC also has been demonstrated to affect noradrenergic (47,48), serotonergic (49), and peptidergic neurons (50), including those of luteinizing hormone releasing hormone (LHRH), which are involved, directly or indirectly, in the mediation of sexual receptivity in female rodents (51,52). ICV administration of THC elevated LHRH content in the MBH within 30 min followed by a decrease at 60 min, concurrent with lowered plasma LH levels in male rats (53).…”

Identification of Endocannabinoids and Cannabinoid CB₁ Receptor mRNA in the Pituitary Gland

“…This may indicate both that the effect of Δ 9 -THC or anandamide stimulating ACTH secretion is mediated by a mechanism other than the activation of CB 1 receptors, and that these receptors are located in anterior pituitary cells other than corticotropes. Lactotropes would be one of the alternative candidates because of the marked effects of cannabinoids on PRL secretion [1, 2, 3, 4, 5, 7]. In addition, although previous studies demonstrated that Δ 9 -THC was unable to alter PRL secretion from incubated pituitary glands [27], thus indicating that the effects of cannabinoids on PRL secretion would be produced through the hypothalamus, we have preliminary evidence that anandamide affects PRL secretion in vitro from dispersed anterior pituitary cells [44].…”

“…Administration of Δ 9 -tetrahydrocanabinol (Δ 9 -THC), the main psychoactive principle of Cannabis sativa preparations, or of other natural or synthetic cannabinoids, decreased prolactin (PRL) and gonadotropin secretion, but increased adrenocorticotropic hormone (ACTH) release from the anterior pituitary gland in rodents [1, 2, 3, 4, 5, 6, 7]. Moreover, anandamide, the first discovered endogenous ligand of cannabinoid receptors [8], is able to produce the same effects [7, 9, 10, 11, 12], thus indicating that endogenous cannabinoids may play a physiological role in neuroendocrine control.…”

The endocannabinoid pathway and the female reproductive organs

“…The primary negative effects are ascribed to a hypothalamic action, although some of these down-regulating influences may be mediated directly at the level of the pituitary and the ovary. At systemic level, cannabinoids are able to modulate the hypothalamic-pituitary-gonadal axis and they have been shown to down-regulate blood LH levels, by indirectly modifying GNRH secretion (Murphy et al 1990). In vitro studies on rats have also demonstrated that D 9 -THC exerts a direct inhibitory effect on both folliculogenesis (Adashi et al 1983) and ovulation (El-Talatini et al 2008).…”