Effects of drug history on the acquisition of responding maintained by GBR 12909 in rhesus monkeys.

Abstract

The reinforcing effects of cocaine have been associated with its actions at the dopamine reuptake site. Previous studies have shown that selective dopamine reuptake inhibitors can attenuate cocaine self-administration in animals, suggesting that they may serve as pharmacotherapeutic agents. In order to assess the potential reinforcing effects of one of these agents, the acquisition and maintenance of GBR 12909 self-administration were studied in different groups of rhesus monkeys (Macaca mulatta) that were either experimentally naive or experienced with respect to the self-administration of cocaine or GBR 12909. Lever-pressing was maintained under a multiple FR30 schedule with alternating components of either food or drug presentation. Experimentally naive monkeys failed to self-administer low doses of GBR 12909 (3-30 mu g/kg per injection). However, after a history of cocaine self-administration, GBR 12909 (56 mu g/kg per injection and then 30 mu g/kg per injection) maintained numbers of drug deliveries similar to those maintained by cocaine. When another group of experimentally-naive monkeys was initially exposed to GBR 12909 self-administration, 56 mu g/kg per injection failed to maintain responding. However, subsequent exposure to 100 mu g/kg per injection established GBR 12909 self-administration, and high levels of responding were sustained later when the unit dose was decreased to 30 mu g/kg per injection. In monkeys with prior experience with cocaine self-administration (approximately 75 sessions) unit doses of either 30 mu g/kg per injection or 56 mu g/kg per injection GBR 12909 maintained responding. In another group of monkeys with a more extensive history of cocaine self-administration (approximately 320 sessions), unit doses of either 10 mu g/kg per injection or 30 mu g/kg per injection GBR 12909 maintained responding. These results show that drug-maintained responding can be established with higher unit doses of GBR 12909. After exposure to these higher, more effective doses of GBR 12909, or effective doses of cocaine, lower doses of GBR 12909 are more likely to support drug-maintained responding.