CHARACTERIZATION OF THE ACUTE ENDOCRINE ACTIONS OF DROXY-DELTA(8)-TETRAHYDROCANNABINOL-DIMETHYLHEPTYL (HU-210), A POTENT SYNTHETIC CANNABINOID IN RATS

In the present study we have characterized the effects of the acute ad ministration of the synthetic droxy-Delta(8)-tetrahydrocannabinol-dime thylheptyl (HU-210, 4, 20 and 100 mu g/kg), on the secretion of prolac tin, growth hormone, luteinizing hormone, follicle-stimulating hormone , adrenocorticotropic hormone and corticosterone in adult male rats. H U-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 revea led a dose-dependent activation of the pituitary-adrenal axis after ac ute exposure to HU-210. Plasma prolactin levels reflected a biphasic a ction 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 t his hormone. The time course of the endocrine effects of HU-210 was ex amined using the 20 mu g/kg dose and was found to parallel the onset o f 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 i nduced activation of tubero-infundibular dopaminergic neurons, as refl ected by the decrease in hypothalamic contents of dopamine in both mal es and females in the afternoon of the proestrus phase. The actions of HU-210 during early postnatal development revealed a delayed maturati on 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) 1 998 Elsevier Science B.V.