Bupropion enhances brain reward function and reverses the affective and somatic aspects of nicotine withdrawal in the rat

Abstract

Bupropion acts on multiple levels to alter brain reward circuits influenced by nicotine, in addition to reducing the expression of somatic signs of withdrawal. First, bupropion, unlike other antidepressants, increases brain reward function under baseline conditions in non-withdrawing subjects. Second, at low doses bupropion blocks the rewarding effects of nicotine. Third, bupropion reverses the negative affective aspects of nicotine withdrawal. Such actions are likely to act in concert to mediate the unique anti-smoking properties of bupropion.

Bupropion dose-dependently reverses nicotine withdrawal deficits in contextual fear conditioning

“…Research has shown that bupropion may facilitate smoking cessation by reducing some symptoms of nicotine withdrawal, such as somatic symptoms or alterations of reinforcement and reward Cryan et al, 2003). However, the effects of bupropion on deficits in learning and memory that occur during nicotine withdrawal remain unknown.…”

“…Cryan and colleagues (2003) reported that a low dose of bupropion blocked the acute nicotine enhancement of ICSS and also reversed the decrease in ICSS when rats were withdrawn from chronic nicotine. In addition, rats withdrawn from chronic nicotine exhibited somatic signs of nicotine withdrawal such as writhing or abdominal constrictions, and bupropion dose-dependently reversed these symptoms (Cryan et al, 2003;Malin et al, 2006). Malin and colleagues (2006) have also found that bupropion can reverse nicotine withdrawal-related conditioned place aversion.…”

“…Furthermore, atomoxetine (a norepinephrine reuptake inhibitor) is also effective in ameliorating nicotine withdrawal-associated deficits in contextual fear conditioning (Davis and Gould, 2007). The effects of bupropion on other symptoms of nicotine withdrawal, such as somatic symptoms or alterations of reward and reinforcement Cryan et al, 2003), suggest that it may be effective in reversing nicotine withdrawal-associated deficits in learning.…”

Genetic variability in nicotinic acetylcholine receptors and nicotine addiction: Converging evidence from human and animal research

“…Withdrawal-related decreases in the brain reward system in humans has been modeled using the intracranial self stimulation (ICSS) procedure, in which rats press a lever to deliver electrical stimulation to reward-related brain areas. Nicotine withdrawal increases ICSS threshold [26,81,156]. Thus, several nicotine withdrawal symptoms reported in humans have been modeled and studied in rodents.…”

Effects of NPY and the specific Y1 receptor agonist [d-His26]-NPY on the deficit in brain reward function and somatic signs associated with nicotine withdrawal in rats

“…The rats were habituated to the observation chamber for 5 minutes per day on 3 consecutive days prior to testing. The following somatic signs were recorded based on checklist of nicotine abstinence signs: body shakes, cheek tremors, escape attempts, eye blinks, gasps, genital licks, head shakes, ptosis, teeth chattering, writhes and yawns (Cryan et al, 2003;Malin et al, 1992). Ptosis was counted once per minute if present continuously.…”