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
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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