2009 5 Nov

Bupropion Attenuates Methamphetamine Self-control In Adult Male Rats

Zyban Sr without prescription 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 self-control study, rats were surgically prepared with indwelling jugular catheters and trained to self-administer methamphetamine under an FR5 schedule. A separate member 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 0.025–0.1 mg/kg methamphetamine; sucrose deliveries were only reduced with the high zyban sr 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.

Bupropion is an antidepressant and smoking cessation aid. Limited toxicological information exists for intentional and unintentional bupropion-only exposures. A retrospective review of all bupropion-only exposures reported to the Nicotine Exposure Surveillance System from 1998 through 1999 was conducted. Data for the three bupropion products, Wellbutrin, Wellbutrin SR, and Zyban,next term included demographics, reason for exposure, clinical effects, therapy, and medical outcome. A total of 7,348 bupropion-only exposures were reported: 56% female and 61% unintentional.

The majority of exposures involved Wellbutrin SR; however, Wellbutrin exposures involved a higher percentage of intentional overdoses and serious clinical effects. Clinical effects related to bupropion were noted in 2,247 (31%) exposures; 8% of all children 6-years-old compared to 46% of all teenagers. Seizures developed in 15% of all intentional exposures. Cardiovascular disturbances were extremely uncommon after overdose. The majority of unintentional bupropion-only exposures result in minimal or no clinical toxicity; however, a significant number of intentional overdoses result in seizures.

Zyban Sr without prescription, a tobacco-cessation product, shares discriminative stimulus effects with cocaine and methamphetamine. The discriminative stimulus effects of these drugs, in turn, overlap with those of nicotine. This study investigated the overlap in discriminative stimulus effects of bupropion and tobacco. Rats were trained to discriminate 0.4 mg/kg (−)-nicotine from saline in 2-lever drug discrimination.

Both nicotine and bupropion substituted for nicotine; however, nicotine’s effects were blocked by the nicotinic antagonist mecamylamine, whereas those of bupropion were not. These results suggest that bupropion may be producing its nicotine-like discriminative stimulus effects through a different mechanism than nicotine. Given bupropion’s shared pharmacology with dopamine transport inhibitors, these effects may be produced in part through bupropion’s actions on dopaminergic neurotransmission.

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