Differential effects of morphine- and cocaine-induced nNOS immunoreactivity in the dentate gyrus of hippocampus of mice lacking μ-opioid receptors

This study investigated the expression of nNOS after repeated morphine or cocaine administration in order to determine if nNOS (neuronal nitric oxide synthase) is involved in the morphine- or cocaine-induced behavioral sensitization in μ-opioid receptor knockout (MOR−/−) mice. Higher numbers of nNOS-positive cells were observed in the dentate gyrus of the hippocampus (DG) of the wild-type (MOR+/+) mice repeatedly treated with either morphine or cocaine than in the saline treated MOR+/+ mice (morphine, +122%; cocaine, +82%). Moreover, the MOR−/− mice also showed significantly higher morphine- or cocaine-induced nNOS expression levels in the DG than in the saline treated MOR+/+ mice (morphine, +234%; cocaine, +54%). The MOR−/− mice showed a significantly higher morphine-induced nNOS expression level (+103%) or a lower cocaine-induced nNOS expression level (+38%) in the DG than in the morphine- or cocaine-treated MOR+/+ mice. These results suggest that morphine and cocaine sensitization is differentially regulated by the μ-opioid receptors in MOR−/− mice via the nNOS systems in the DG.