Injection of SCH 23390 into the ventral tegmental area blocks the development of neurochemical but not behavioral sensitization to cocaine.

Previous studies have indicated that dopamine D-1 receptors in the ventral tegmental area (VTA) may play an important role in the development of sensitization to amphetamine. The present study was designed to determine if D-1 receptors are also important in the development of cocaine-induced behavioral and neurochemical sensitization. Animals received intra-VTA injections of saline or the dopamine D-1 receptor antagonist SCH 23390 (15 nmol/side) 5 min before receiving systemic injections of saline or cocaine (15 mg/kg) on 4 consecutive days. One week later animals were challenged with cocaine. Motor activity and extracellular dopamine concentrations in the nucleus accumbens were monitored on the day the animals received the first of their four daily treatments and/or on the day animals received their cocaine challenge injection. Intra-VTA SCH 23390 attenuated the acute response, but did not alter development of the sensitized motor-stimulant response to cocaine. In contrast to the behavioral data, intra-VTA SCH 23390 blocked both the acute cocaine-induced increase in extracellular dopamine in the nucleus accumbens and development of the sensitized response. These data provide partial support for the role of dopamine D-1 receptors in the VTA in the development of cocaine-induced sensitization. The data also suggest, however, that additional mechanisms may play a role in the development of sensitization.