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

Area of Science:

• Neuroscience
• Pharmacology
• Addiction Research

Background:

• Methamphetamine is a highly addictive psychostimulant with no FDA-approved treatments.
• Developing selective pharmacotherapies to reduce methamphetamine use is a critical unmet medical need.

Purpose of the Study:

• To evaluate GZ-793A (a VMAT-2 inhibitor) and varenicline for their efficacy in reducing methamphetamine self-administration.
• To determine if these agents selectively decrease methamphetamine intake without affecting food-maintained responding.

Main Methods:

• Rats self-administered methamphetamine and food pellets under a multiple schedule of reinforcement.
• GZ-793A or varenicline was administered prior to the multiple schedule sessions.
• Drug effects on intake of both reinforcers were assessed compared to saline controls.

Main Results:

• GZ-793A (5 and 20 mg/kg) significantly reduced methamphetamine intake.
• GZ-793A did not alter food-maintained responding, indicating selectivity.
• Varenicline showed less specific reductions in methamphetamine intake over time.

Conclusions:

• Vesicular monoamine transporter-2 inhibition represents a promising pharmacological strategy for treating methamphetamine use disorders.
• Selective reduction of drug intake without affecting other motivated behaviors is achievable with VMAT-2 inhibitors.