Authors: Kristin M Alvers Joshua S Beckmann Guangrong Zheng Peter A Crooks Linda P Dwoskin Michael T Bardo
Publish Date: 2012/05/26
Volume: 224, Issue: 2, Pages: 255-262
Abstract
The vesicular monoamine transporter 2 VMAT2 has been identified as a potential target for the treatment of methamphetamine METH abuse GZ793A 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 aloneAfter a period of extinction rats were administered GZ793A 15 mg/kg sc 15 min prior to a priming injection of METH or reexposure to cues associated with METH infusions GZ793A also was administered 20 min prior to an injection of METH 05 mg/kg sc or saline to determine its effect on locomotor behaviorPretreatment with GZ793A 15 mg/kg decreased cueinduced reinstatement without demonstrating any response suppressive effects when administered in the absence of reinstating stimuli GZ793A also decreased methamphetamineinduced reinstatement however response suppressant effects of GZ793A were obtained when the compound was presented alone In this latter experiment GZ793A may have reduced responding for the conditioned reinforcing effects of the contingently available cues rather than having nonspecific effects on baseline responding GZ793A had no effect on locomotor activity when administered alone or with METHThis research was supported by the National Institute of Drug Abuse grants DA13519 and DA016176 We thank Emily Denehy for technical assistance The University of Kentucky holds a patent on GZ793A and a potential royalty stream to LPD GZ and PAC may occur consistent with the University of Kentucky policy
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