Amphetamine maintenance differentially modulates effects of cocaine, methylenedioxypyrovalerone (MDPV), and methamphetamine on intracranial self-stimulation and nucleus accumbens dopamine in rats

Abstract

Amphetamine maintenance is effective clinically to reduce the consumption of the monoamine uptake inhibitor cocaine but not of the monoamine releaser methamphetamine, and its effectiveness in treating the abuse of other psychostimulants is not known. The mechanisms for differential amphetamine-maintenance effectiveness to treat different types of psychostimulant abuse are also not known. Accordingly, the present study compared the effects of amphetamine maintenance on abuse-related behavioral and neurochemical effects of cocaine, methamphetamine, and the "bath salts" constituent 3,4-methylenedioxypyrovalerone (MDPV) in rats. In behavioral studies, rats were trained to lever press for electrical brain stimulation in an intracranial self-stimulation (ICSS) procedure. In neurochemical studies, nucleus accumbens (NAc) levels of dopamine (DA) and serotonin (5-HT) were monitored by in vivo microdialysis. Cocaine, methamphetamine, and MDPV each produced dose-dependent ICSS facilitation and increases in NAc DA; cocaine and methamphetamine also increased NAc 5-HT. Amphetamine maintenance (0.32 mg/kg/h × 7 days) produced (1) sustained increases in basal ICSS and NAc DA with no change in NAc 5-HT, (2) blockade of cocaine but not methamphetamine effects on ICSS and NAc DA, and (3) no blockade of cocaine- or methamphetamine-induced increases in NAc 5-HT. Amphetamine maintenance blocked the increases in NAc DA produced by the selective DA uptake inhibitor MDPV, but it did not block MDPV-induced ICSS facilitation. These results show different effects of amphetamine maintenance on behavioral and neurochemical effects of different psychostimulants. The selective effectiveness of amphetamine maintenance to treat cocaine abuse may reflect attenuation of cocaine-induced increases in NAc DA while preserving cocaine-induced increases in NAc 5-HT.