Characterization of the acute endocrine actions of (-)-11-hydroxy-Δ8-tetrahydrocannabinol-dimethylheptyl (HU-210), a potent synthetic cannabinoid in rats

In the present study we have characterized the effects of the acute administration of the synthetic cannabinoid(-)-11-hydroxy-Delta(8)-tetrahydrocannabinol-dimethylheptyl (HU-210, 4, 20 and 100 mu g/kg), on the secretion of prolactin, growth hormone, luteinizing hormone, follicle-stimulating hormone, adrenocorticotropic hormone and corticosterone in adult male rats. HU-210 administration resulted in a dose-dependent inhibition of plasma growth hormone, follicle-stimulating hormone and luteinizing hormone 60 min after the acute intraperitoneal injection, starting at 20 mu g/kg. Plasma adrenocorticotropic hormone and corticosterone levels revealed a dose-dependent activation of the pituitary-adrenal axis after acute exposure to HU-210. Plasma prolactin levels reflected a biphasic action of HU-210: the 4 mu g/kg dose resulted in high prolactin levels and the 20 and 100 mu g/kg doses induced a decrease in the levels of this hormone. The time course of the endocrine effects of HU-210 was examined using the 20 mu g/kg dose and was found to parallel the onset of the immobility and hypothermic effects of this cannabinoid. HU-210 (20 mu g/kg) was also found to block the hormonal surges of luteinizing hormone, follicle-stimulating hormone and prolactin occurring during the afternoon of the proestrus phase in adult female rats. This dose induced activation of tubero-infundibular dopaminergic neurons, as reflected by the decrease in hypothalamic contents of dopamine in both males and females in the afternoon of the proestrus phase. The actions of HU-210 during early postnatal development revealed a delayed maturation of the endocrine response to HU-210, with respect to the behavioral effects. The findings of the present study reveal that HU-210 induces a set of endocrine alterations closely related to those described for natural cannabinoids such as dg-tetrahydrocannabinol but at doses 50-200 times lower than those required for dg-tetrahydrocannabinol. (C) 1998 Elsevier Science B.V.