Prolonged morphine treatment increases rat brain dihydropyridine binding sites: possible involvement in development of morphine dependence

Regulation of L-type Ca²⁺ channels by morphine in rat brain was determined by the binding of [³H]nimodipine. Morphine, administered by subcutaneous pellet implantation, increased the density of [³H]nimodipine binding sites in a time- and dose-dependent manner and this effect was reversible upon removal of the pellets. Increases in these dihydropyridine siteswere localized to the cortex, hippocampus, hypothalamus and brainstem but not to the cerebellum and striatum. Additional experiments were performed to test the ability of different Ca²⁺ channel antagonists to affect naloxone-precipitated withdrawal in morphine-dependent mice and rats. These drugs effectively reduced the incidence of naloxone-induced jumping in mice and several of the withdrawal signs in rats. Taken together, our study underscores the plasticity of brain L-type Ca²⁺ channels and suggests that their upregulation might contribute to morphine dependence.