Varenicline and GZ-793A differentially decrease methamphetamine self-administration under a multiple schedule of reinforcement in rats

• Published in: Behavioural pharmacology Vol. 29; no. 1; pp. 87 - 97
• Main Authors: Kangiser, Megan M, Dwoskin, Linda P, Zheng, Guangrong, Crooks, Peter A, Stairs, Dustin J
• Format: Journal Article
• Language: English
• Published: England Copyright YEAR Wolters Kluwer Health, Inc. All rights reserved 01-02-2018
• ISSN: 0955-8810; 1473-5849
• DOI: 10.1097/FBP.0000000000000340

Methamphetamine is a potent psychostimulant with high abuse rates. Currently, there is no Food and Drug Administration-approved pharmacotherapy for methamphetamine addiction. Ideally, a pharmacotherapy should selectively decrease methamphetamine self-administration without affecting responding for other reinforcers. One way to test this is with the use of a multiple schedule of reinforcement, in which drug and food are available in alternating components within a session. The present study evaluated GZ-793A, a vesicular monoamine transporter-2 inhibitor, and varenicline, a partial agonist at α4β2 and full agonist at α7 nicotinic acetylcholine receptors, for their ability to decrease methamphetamine and food self-administration using a multiple schedule of reinforcement. Male Sprague-Dawley rats self-administered methamphetamine (0.03 mg/kg/intravenous infusion) and food pellets under a multiple schedule of reinforcement. GZ-793A or varenicline was administered before multiple schedule sessions. GZ-793A (5 and 20 mg/kg) significantly decreased methamphetamine intake compared with saline and did not alter food-maintained responding. In contrast, varenicline decreased methamphetamine intake less specifically across time. The results suggest that vesicular monoamine transporter-2 inhibition may be a viable pharmacological target for the treatment of methamphetamine-use disorders.