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.
Bibliographical noteFunding Information:
This work was supported by Korea Research Foundation Grant (2003-041-E00327) and Brain Research Center of the 21st Century Frontier Research Program (M103KV010008 05K2201 00830).
- Knockout mice
- μ-Opioid receptors