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

1998; Elsevier BV; Volume: 344; Issue: 1 Linguagem: Inglês

10.1016/s0014-2999(97)01560-4

1879-0712

José Luis Martı́n-Calderón, Raúl M. Muñoz, María Ángeles Villanúa, Ignacio del Arco, José L. Moreno, Fernando Rodrı́guez de Fonseca, Miguel Navarro,

Neuroscience of respiration and sleep

In the present study we have characterized the effects of the acute administration of the synthetic cannabinoid (−)-11-hydroxy-Δ8-tetrahydrocannabinol-dimethylheptyl (HU-210, 4, 20 and 100 μg/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 μg/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 μg/kg dose resulted in high prolactin levels and the 20 and 100 μg/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 μg/kg dose and was found to parallel the onset of the immobility and hypothermic effects of this cannabinoid. HU-210 (20 μg/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 Δ9-tetrahydrocannabinol but at doses 50–200 times lower than those required for Δ9-tetrahydrocannabinol.