Dopamine receptor subsensitivity in the substantia nigra after chronic morphine treatment in rats

Several classes of 5-HT and dopamine (DA) receptor binding sites, and the levels of 5-HT, 5-hydroxyindoleacetic acid (5-HIAA), DA and dihydroxyphenylacetic acid (DOPAC) were examined in various brain regions 24 h after a 10-day treatment with morphine (2 X 15 mg/kg s.c. daily) in adult rats. Quantitative autoradiography of receptor binding sites revealed only a significant reduction of [3H]SCH-23390 and [3H]spiperone binding to D-1 and D-2 sites, respectively, in the substantia nigra pars compacta of morphine-treated rats. 5-HT and 5-HIAA levels remained unchanged in the substantia nigra and striatum, but the nigral levels of DA and DOPAC and the levels of DOPAC in the striatum were reduced significantly by morphine treatment. Apomorphine, at a dose (0.05 mg/kg s.c.) known to stimulate DA autoreceptors, decreased nigral and striatal DOPAC levels in controls but not in morphine-treated rats. It is concluded that chronic morphine treatment probably induces a down regulation of nigral D-1 and D-2 binding sites and reduces the negative feed-back mechanisms triggered by DA autoreceptors.