Obese Zucker rat is a model of genetic obesity characterized by hyperphagia, diabetes and increased glucocorticoid levels. Endocannabinoid system is involved in the physiological regulation of appetite, through the action of endogenous endocannabinoids on CB1 cannabinoid receptors. CB1 cannabinoid receptor phosphorilation generates inactivation. The aim of the present work was to describe the CB1 and phosphorylated CB1 cannabinoid receptor regional prosencephalic expression in obese Zucker rats, with respect to their lean littermates. Several brain cortex regions were immunostained for CB1 and phosphorylated CB1 cannabinoid receptors using avidin-peroxidase technique and 3,3´-diaminobenzidine as chromogen. Results were analyzed with the aid of a computerized image analysis system. Student´s T test was used for comparisons between treatment and control values (mean + S.E.M.). p values<0.05 were considered as statistically significant.

Obese Zucker rats showed a significant increase in the numbers of neural cells positively immunostained for CB1 and phosphorylated CB1 receptors in several prosencephalic regions, with respect to lean Zucker rats. These results suggest an increased activity of endocannabinoid system in this model, which could be involved in hyperphagia, and reinforce the possible role of CB1 cannabinoid receptor as a pharmacological target for appetite management in obese patients.

This work has been supported by a UPV/EHU grant (1/UPV00081.327-E-15320/2003). We would like to thank Juan Manuel Rodríguez Robledo for his technical assistance.