Wojnicki F H, Glowa J R
Laboratory of Medicinal Chemistry, NIDDK, National Institutes of Health, Bethesda, MD 20892-5550, USA.
Psychopharmacology (Berl). 1996 Jan;123(1):34-41. doi: 10.1007/BF02246278.
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.
可卡因的强化作用与其作用于多巴胺再摄取位点有关。先前的研究表明，选择性多巴胺再摄取抑制剂可减弱动物对可卡因的自我给药行为，这表明它们可能用作药物治疗剂。为了评估其中一种药物的潜在强化作用，在不同组的恒河猴（猕猴）中研究了GBR 12909自我给药行为的获得和维持情况，这些恒河猴要么是实验新手，要么有过可卡因或GBR 12909自我给药的经历。在一个多重FR30程序下维持杠杆按压行为，该程序交替呈现食物或药物。实验新手猴子未能自我给药低剂量的GBR 12909（每次注射3 - 30μg/kg）。然而，在有过可卡因自我给药经历后，GBR 12909（每次注射56μg/kg，然后每次注射30μg/kg）维持的给药次数与可卡因维持的给药次数相似。当另一组实验新手猴子最初接触GBR 12909自我给药时，每次注射56μg/kg未能维持反应。然而，随后接触每次注射100μg/kg建立了GBR 12909自我给药行为，并且当单位剂量降至每次注射30μg/kg时，高水平的反应后来得以维持。在有过可卡因自我给药经历（约75次实验）的猴子中，每次注射30μg/kg或56μg/kg的GBR 12909单位剂量维持了反应。在另一组有更广泛可卡因自我给药经历（约320次实验）的猴子中，每次注射10μg/kg或30μg/kg的GBR 12909单位剂量维持了反应。这些结果表明，较高单位剂量的GBR 12909可建立药物维持的反应。在接触这些较高、更有效的GBR 12909剂量或有效的可卡因剂量后，较低剂量的GBR 12909更有可能支持药物维持的反应。
