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Psychopharmacology (Berl). 2012 Nov;224(2):255-62. doi: 10.1007/s00213-012-2748-3. Epub 2012 May 26.

The effect of VMAT2 inhibitor GZ-793A on the reinstatement of methamphetamine-seeking in rats.

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1
Department of Psychology, University of Kentucky, 106b Kastle Hall, Lexington, KY 40506, USA.

Abstract

RATIONALE:

The vesicular monoamine transporter 2 (VMAT2) has been identified as a potential target for the treatment of methamphetamine (METH) abuse. GZ-793A is a potent and selective VMAT2 inhibitor that has been shown to block the primary and conditioned reinforcing effects of METH, while demonstrating no abuse liability when given alone.

OBJECTIVES:

The aim of the current study was to determine if GZ-793A attenuates METH- or cue-induced reinstatement of METH-seeking after a period of extinction. The effect of acute GZ-793A on locomotor activity also was assessed.

METHODS:

After a period of extinction, rats were administered GZ-793A (15 mg/kg, s.c.) 15 min prior to a priming injection of METH or re-exposure to cues associated with METH infusions. GZ-793A also was administered 20 min prior to an injection of METH (0.5 mg/kg, s.c.) or saline to determine its effect on locomotor behavior.

RESULTS:

Pretreatment with GZ-793A (15 mg/kg) decreased cue-induced reinstatement, without demonstrating any response suppressive effects when administered in the absence of reinstating stimuli. GZ-793A also decreased methamphetamine-induced reinstatement; however, response suppressant effects of GZ-793A were obtained when the compound was presented alone. In this latter experiment, GZ-793A may have reduced responding for the conditioned reinforcing effects of the contingently available cues rather than having nonspecific effects on baseline responding. GZ-793A had no effect on locomotor activity when administered alone or with METH.

CONCLUSIONS:

GZ-793A and related VMAT2 inhibitors may be promising leads for reducing the risk of relapse to METH use following exposure to drug-associated cues.

PMID:
22638813
PMCID:
PMC3680349
DOI:
10.1007/s00213-012-2748-3
[Indexed for MEDLINE]
Free PMC Article
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