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.
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Acknowledgements
The research reported in this publication was supported by the National Institute on Drug Abuse of the National Institutes of Health under Award Number R01 DA033930 and T32 DA007027. The content is solely the responsibility of the author and does not necessarily represent the official views of the National Institutes of Health.
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ARJ conducted all the experiments, the initial graphing and analysis of all the data, and drafted the text. MLB supervised the microdialysis studies, SSN supervised the ICSS studies, and DES supervised the receptor binding studies. MLB, SSN, and DES contributed to the experimental design and generation of final data analysis, graphs, and text. All authors approved the final text.
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Johnson, A.R., Banks, M.L., Selley, D.E. et al. Amphetamine maintenance differentially modulates effects of cocaine, methylenedioxypyrovalerone (MDPV), and methamphetamine on intracranial self-stimulation and nucleus accumbens dopamine in rats. Neuropsychopharmacol 43, 1753–1762 (2018). https://doi.org/10.1038/s41386-018-0071-3
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DOI: https://doi.org/10.1038/s41386-018-0071-3
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