The effects of varenicline on methamphetamine self-administration and drug-primed reinstatement in female rats

• Female Sprague-Dawley rats readily self-administered methamphetamine.
• Varenicline attenuated responding during self-administration.
• Female rats displayed robust reinstatement of active lever pressing.
• Reinstatement responding was increased following varenicline administration.

While research has revealed heightened vulnerability to meth addiction in women, preclinical models rarely use female subjects when investigating meth seeking and relapse. The goal of the present study was to examine the effects of varenicline (Chantix®), a partial α4β2 and full α7 nicotinic acetylcholine receptor agonist, on meth self-administration and reinstatement in female rats. Sprague-Dawley rats were surgically implanted with an indwelling jugular catheter. Half of the rats were then trained to self-administer meth (0.056 mg/kg/infusion) on a variable ratio 3 schedule of reinforcement; the other half earned intravenous saline during daily, 2 h sessions. When responding stabilized, varenicline (0.0, 0.3, 1.0, 3.0 mg/kg) was tested to determine how it altered meth taking. Varenicline was probed on 4 test days; each test separated by 2 standard self-administration sessions to assure responding remained stable. Following this testing was 15 extinction sessions. Twenty-four hours after the last extinction session were four consecutive days of meth-primed reinstatement. The same 4 doses of varenicline were examined to determine how it altered reinstatement triggered by 0.3 mg/kg meth (IP). Rats readily self-administered meth. The higher doses of varenicline did not affect meth-taking in a specific fashion as active lever pressing was also slightly reduced in rats that has access to saline in the self-administration phase. Female rats displayed robust meth-primed reinstatement. Notably, the lower doses of varenicline increased meth-primed reinstatement. This amplified susceptibility to reinstatement (i.e., relapse) may be an impediment for the use of varenicline as a therapeutic to treat meth use disorder.