Involvement of nitric oxide in morphine-induced c-Fos expression in the rat striatum

Induction of expression of immediate-early gene c-Fos in the striatum is a common effect of many drugs of abuse, including morphine. Previous studies have shown that the morphine-mediated c-Fos response is attenuated by antag onists of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor. Ot her evidence suggests that the NDMA receptor may be coupled to the enzyme n euronal nitric oxide synthase (nNOS). NMDA receptor-mediated increases in i ntracellular calcium can activate nNOS, which catalyzes the formation of th e signaling molecule nitric oxide. Because activation of NMDA receptors med iates morphine-induced c-Fos expression, we tested the hypothesis that acti vation of nNOS is involved in this cascade. Male rats were injected with th e nNOS-selective inhibitor 7-nitroindazole (7-NI) or vehicle 30 min prior t o injection of morphine sulfate or vehicle. Two hours later they were perfu sed with fixative and the brains removed for immunocytochemical analysis fo r c-Fos, Morphine induced c-Fos expression in the striatum, cerebral cortex , and midline/intralaminar nuclei of thalamus. Expression in the striatum, but not thalamus or cortex, was significantly blocked by 7-NI. Double-label immunocytochemistry revealed no co-localization of c-Fos and nNOS in any b rain region. These results support a role for nNOS in the neural circuits a ctivated by morphine. (C) 2001 Elsevier Science Inc.