Microinjections of Sch-23390 into the ventral tegmental area and substantia nigra pars reticulata attenuate the development of sensitization to the locomotor activating effects of systemic amphetamine.

Pre-exposure of rats to systemic injections of D-amphetamine sulfate in the presence of bilateral injections of Sch-23390 (0.5 or 1.0 micrograms/side) into the ventral tegmental area (VTA) attenuated the acute locomotor effects of amphetamine and blocked the development of sensitization to amphetamine in a test when only amphetamine was administered, in a dose-dependent manner. Similar, but less potent, effects were observed following injections into substantia nigra pars reticulata. These findings suggest that dopamine released from somatodendritic regions brings about changes in local circuitry in the VTA that underlie the development of sensitization to amphetamine, and that Sch-23390 acts at D1 receptors in these regions to block these changes.