Oral administration of GZ-793A, a VMAT2 inhibitor, decreases methamphetamine self-administration in rats.

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TitleOral administration of GZ-793A, a VMAT2 inhibitor, decreases methamphetamine self-administration in rats.
Publication TypeJournal Article
Year of Publication2013
JournalPharmacology, biochemistry, and behavior
Volume112
Pagination29-33
ISSN0091-3057
Abstract

Despite the high prevalence of use of methamphetamine (METH), there is no FDA-approved pharmacological treatment available currently for METH addiction. The vesicular monoamine transporter (VMAT2) has been proposed as a novel target to treat METH abuse. GZ-793A, a lobelane analog and selective VMAT2 inhibitor, has been shown previously to decrease METH self-administration specifically when administered via the subcutaneous route in rats. Since oral administration is the preferred clinical route, the present experiments determined if oral administration of GZ-793A would decrease specifically METH self-administration. Experiments 1 and 2 assessed the dose-effect functions of oral administration of GZ-793A (30-240 mg/kg) on intravenous METH self-administration and food-maintained responding, respectively. Experiments 3 and 4 assessed the time-course (20-180 min pretreatment) of oral administration of GZ-793A on METH self-administration and food-maintained responding, respectively. Oral administration of GZ-793A dose-dependently decreased METH self-administration, with the highest dose (240 mg/kg) producing an 85% decrease compared to control baseline. The decrease in METH self-administration produced by GZ-793A (120 mg/kg) lasted at least 180 min. In contrast, GZ-793A failed to alter food-maintained responding at any of the doses or pretreatment intervals tested. The oral effectiveness and the specificity of GZ-793A to decrease methamphetamine self-administration support the feasibility of developing VMAT2 inhibitors as treatments for METH abuse.

URLhttps://linkinghub.elsevier.com/retrieve/pii/S0091-3057(13)00222-0
DOI10.1016/j.pbb.2013.09.006
Short TitlePharmacol Biochem Behav
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