Characterization of the acute endocrine actions of (-)-11-hydroxy-delta8-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-delta8-tetrahydrocannabinol-dimethylheptyl (HU-210, 4, 20 and 100 microg/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 microg/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 microg/kg dose resulted in high prolactin levels and the 20 and 100 microg/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 microg/kg dose and was found to parallel the onset of the immobility and hypothermic effects of this cannabinoid. HU-210 (20 microg/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 delta9-tetrahydrocannabinol but at doses 50-200 times lower than those required for delta9-tetrahydrocannabinol.
Martín-Calderón
J L
JL
Departamento de Psicobiología, Facultad de Psicología, Instituto Complutense de Drogodependencias, Universidad Complutense de Madrid, Spain.
Muñoz
R M
RM
Villanúa
M A
MA
del Arco
I
I
Moreno
J L
JL
de Fonseca
F R
FR
Navarro
M
M
D000818:Animals; D002395:Catecholamines / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D013759:Dronabinol / Q000031:analogs & derivatives* / Q000494:pharmacology; D004703:Endocrine System / Q000187:drug effects* / Q000378:metabolism; D004971:Estrus / Q000187:drug effects; D005260:Female; D006728:Hormones / Q000378:metabolism*; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D002395:Catecholamines; D006728:Hormones; D013759:Dronabinol; C062018:HU 211