Immunohistochemical localization of CB 1 cannabinoid receptors in frontal cortex and related limbic areas in obese Zucker rats: Effects of chronic fluoxetine treatment

Abstract

In the present study, we report on the application of two specific polyclonal antibodies to different intracellular domains of the CB 1 cannabinoid receptor to define the expression of the neural CB 1 cannabinoid receptor at the histochemical level in frontal cortex and related limbic areas of the obese Zucker rats. Higher levels of CB 1 receptor expression in frontal, cingulated and piriform cortex, without differences in temporal, parietal and occipital cortex, were observed in obese Zucker rats, with respect to their lean littermates. CB 1 phosphorylated receptor (CB 1-P) levels were also higher in frontal, temporal, parietal and occipital cortex in obese rats with respect to lean controls. Potential involvement of brain cortical CB 1 cannabinoid receptors in the long-term effects of fluoxetine was studied. Experimental animals were administered with fluoxetine (10 mg/kg, i.p.) daily for 3 weeks, whereas the control group was given 0.9% NaCl solution. In obese Zucker rats, a significant decrease in CB 1 receptor levels, measured by western blot, was observed in brain cortex after fluoxetine treatment. Immunostaining for CB 1 receptor expression was also carried out, showing a significant decrease in the density of neural cells positive for CB 1 receptor in frontal, cingulate and piriform cortex, without changes in parietal, temporal and occipital regions. Regional prosencephalic immunostaining for CB 1-P receptor level showed a significant decrease in the density of stained neural cells in frontal, temporal and parietal cortex, without changes in cingulated, piriform and occipital cortex. These results suggest the involvement of endocannabinoid system in the chronic effects of fluoxetine, especially in the frontal cortex.