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

Carrie E. Wilmouth, Guangrong Zheng, Peter A. Crooks, Linda P. Dwoskin, Michael T. Bardo

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

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.

Original languageEnglish
Pages (from-to)29-33
Number of pages5
JournalPharmacology Biochemistry and Behavior
Volume112
DOIs
StatePublished - 2013

Bibliographical note

Funding Information:
We thank Emily Denehy and William McCuddy for their technical assistance. This work was supported by the NIH grants U01 DA13519 and T32 DA01617 .

Keywords

  • Dopamine
  • Methamphetamine
  • Self-administration
  • VMAT2

ASJC Scopus subject areas

  • Biochemistry
  • Toxicology
  • Pharmacology
  • Clinical Biochemistry
  • Biological Psychiatry
  • Behavioral Neuroscience

Fingerprint

Dive into the research topics of 'Oral administration of GZ-793A, a VMAT2 inhibitor, decreases methamphetamine self-administration in rats'. Together they form a unique fingerprint.

Cite this