Atypical dopamine transporter inhibitors attenuate compulsive-like methamphetamine self-administration in rats
Autor: | Jianjing Cao, Janaina C. M. Vendruscolo, Rana Rais, Alexandra J. Gadiano, Leandro F. Vendruscolo, Brooke E. Schmeichel, Rachel D. Slack, Chelsea P. Ho, Gianluigi Tanda, Brendan J. Tunstall, Amy Hauck Newman, George F. Koob, Barbara S. Slusher |
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Rok vydání: | 2018 |
Předmět: |
Male
0301 basic medicine Drug Time Factors media_common.quotation_subject Modafinil Self Administration Pharmacology Article Methamphetamine Pharmacological treatment 03 medical and health sciences Cellular and Molecular Neuroscience chemistry.chemical_compound Saccharin 0302 clinical medicine mental disorders Animals Medicine Benzhydryl Compounds Rats Wistar Dopamine transporter media_common Analysis of Variance Dopamine Plasma Membrane Transport Proteins Dose-Response Relationship Drug Propylamines biology business.industry Wakefulness-Promoting Agents Meth Rats 030104 developmental biology chemistry Compulsive Behavior biology.protein Conditioning Operant Dopamine Antagonists Central Nervous System Stimulants Drug intoxication business Self-administration 030217 neurology & neurosurgery medicine.drug |
Zdroj: | Neuropharmacology. 131:96-103 |
ISSN: | 0028-3908 |
Popis: | Methamphetamine (METH) is a highly addictive drug, but no pharmacological treatment is yet available for METH use disorders. Similar to METH, the wake-promoting drug (R)- modafinil (R-MOD) binds to the dopamine transporter (DAT). Unlike METH, R-MOD is not a substrate for transport by DAT and has low abuse potential. We tested the hypothesis that the atypical DAT inhibitor R-MOD and compounds that are derived from Modafinil would decrease METH intake by reducing the actions of METH at the DAT. We tested the effects of systemic injections of R-MOD and four novel Modafinil-derived ligands with increased DAT affinity (JJC8-016, JJC8-088, JJC8-089, and JJC8-091) on intravenous (i.v.) METH self-administration in rats that were allowed short access (ShA; 1 h) or long access (LgA; 6 h) to the drug. ShA rats exhibited stable METH intake over sessions, whereas LgA rats exhibited an escalation of drug intake. R-MOD decreased METH self-administration in ShA and LgA rats (in the 1(st) hour only). JJC8-091, and JJC8-016 decreased METH self-administration in both ShA and LgA rats. JJC8- 089 decreased METH self-administration in LgA rats only, whereas JJC8-088 had no effect on METH self-administration in either ShA or LgA rats. These findings support the potential of atypical DAT inhibitors for the treatment of METH use disorders and suggest several novel compounds as candidate drugs. |
Databáze: | OpenAIRE |
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