Bupropion attenuates methamphetamine self-administration in adult male rats

Abstract

Bupropion is a promising candidate medication for methamphetamine use disorder. As such, we used a preclinical model of drug-taking to determine the effects of bupropion on the reinforcing effects of methamphetamine (0.025, 0.05 or 0.1 mg/kg/infusion). Specificity was determined by investigating the effects of bupropion on responding maintained by sucrose. In the selfadministration study, rats were surgically prepared with indwelling jugular catheters and trained to self-administer methamphetamine under an FR5 schedule. A separate group of rats was trained to press a lever for sucrose. Once responding stabilized, rats were pretreated with bupropion (0, 10, 30 and 60 mg/kg IP) 5 min before chamber placement in a unique testing order. Following acute testing, rats were then repeatedly pretreated with 30 and 60 mg/kg bupropion. Acute treatments of bupropion dose dependently reduced drug intake for 0.025 to 0.1 mg/kg methamphetamine; sucrose deliveries were only reduced with the high bupropion dose. Repeated exposure to 60 mg/ kg bupropion before the session resulted in a consistent decrease in methamphetamine intake (0.05 and 0.1 mg/kg) and sucrose deliveries. Considered together, this pattern of findings demonstrates that bupropion decreases responding for methamphetamine, but the effects are only somewhat specific.

Effects of Environmental Manipulations and Treatment with Bupropion and Risperidone on Choice between Methamphetamine and Food in Rhesus Monkeys

“…Acute bupropion pretreatment significantly decreased rates of methamphetaminemaintained responding at some methamphetamine doses but did not significantly alter methamphetamine intake (Schindler et al, 2011). In rat methamphetamine selfadministration studies, both acute and repeated bupropion pretreatment decreased methamphetamine-maintained responding (Reichel et al, 2008;Reichel et al, 2009). However, tolerance developed to these bupropion effects during repeated administration (Reichel et al, 2009).…”

“…The second aim was to determine 7-day treatment effects of two compounds, bupropion and risperidone, that have been examined in human laboratory and clinical trials as candidate pharmacotherapies for methamphetamine addiction. The monoamine uptake inhibitor bupropion was selected because bupropion (1) antagonizes methamphetamineinduced DA efflux in vitro (Simmler et al, 2013), (2) treatment attenuates methamphetamine reinforcement in preclinical methamphetamine self-administration studies (Reichel et al, 2008;Reichel et al, 2009;Schindler et al, 2011), (3) blunts methamphetamine subjective effects in human laboratory studies (Newton et al, 2006), and (4) has shown weak or no efficacy in double-blind placebo-controlled clinical trials (Elkashef et al, 2008;Heinzerling et al, 2014;Shoptaw et al, 2008). Risperidone was selected as a representative DA antagonist medication, because it is a nonselective DA D1-and D2-family antagonist with high D2-family occupancy (Lako et al, 2013).…”

The antidepressant bupropion exerts alleviating properties in an ovariectomized osteoporotic rat model

“…Animals were allocated into four groups, ten animals each, as follows: (1) [40,41] . One week after the ovariectomy and sham operations, treatment with bupropion was started.…”

Interactions between Bupropion and 3,4-Methylenedioxymethamphetamine in Healthy Subjects

“…Using previously published methods (Simmler et al, 2013b), we also confirmed that bupropion inhibited the human DA, NE, and 5-HT transporter with IC 50 values of 1.6, 18, and .100 mM, respectively. Bupropion has been shown to inhibit the amphetamine-and methamphetamine-induced release of DA in vitro (Gruner et al, 2009;Simmler et al, 2013b) and decrease methamphetamine self-administration in rats (Reichel et al, 2009) and monkeys (Schindler et al, 2011). Bupropion also reduced methamphetamine-induced subjective and cardiostimulant effects in humans (Newton et al, 2005(Newton et al, , 2006 and may reduce drug use in subsets of methamphetamine users (Elkashef et al, 2008;Heinzerling et al, 2014).…”