Bupropion increases striatal vesicular monoamine transport

Rau, Kristi S.; Birdsall, Elisabeth; Hanson, Jarom E.; Johnson-Davis, Kamisha L.; Carroll, F. Ivy; Wilkins, Diana G.; Gibb, James W.; Hanson, Glen R.; Fleckenstein, Annette E.

doi:10.1016/j.neuropharm.2005.05.004

Cited by 65 publications

(51 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These effects appear to be due to the ability of bupropion to inhibit the inward transport of methamphetamine, thus limiting the ability of methamphetamine to displace DA from vesicular stores. In a recent report (Rau et al, 2005), bupropion rapidly, reversibly, and dose dependently increased vesicular DA uptake, an effect associated with vesicular monoamine transporter-2 protein redistribution. Of interest, the bupropion-induced increases in vesicular DA uptake were prevented by pretreatment with eticlopride, a DA D 2 receptor antagonist, but not by SCH 23390, a DA D 1 receptor antagonist.…”

Section: Discussionmentioning

confidence: 90%

Bupropion Reduces Methamphetamine-Induced Subjective Effects and Cue-Induced Craving

Newton

Roache

Garza

et al. 2005

Neuropsychopharmacol

141

126

View full text Add to dashboard Cite

Bupropion is an antidepressant with stimulant properties, which inhibits the reuptake of dopamine (DA) and norepinepherine, and is purported to enhance DA neurotransmission. Bupropion is considered an appealing candidate medication for the treatment of methamphetamine dependence. The current laboratory study was set forth to assess the impact of bupropion treatment on the subjective effects produced by methamphetamine in the laboratory. We also assessed the effects of bupropion treatment on craving elicited by exposure to videotaped methamphetamine cues. A total of 26 participants were enrolled and 20 completed the entire study (n ¼ 10 placebo and n ¼ 10 bupropion, parallel groups design). Bupropion treatment was associated with reduced ratings of 'any drug effect' (po0.02), and 'high' (po0.02) following methamphetamine administration. There was also a significant bupropion-by-cue exposure interaction on General Craving Scale total score (po0.002), and on the Behavioral Intention subscale (po0.001). Overall, the data reveal that bupropion reduced acute methamphetamine-induced subjective effects and reduced cue-induced craving. Importantly, these data provide a rationale for the evaluation of bupropion in the treatment of methamphetamine dependence.

show abstract

Section: Discussionmentioning

confidence: 90%

Bupropion Reduces Methamphetamine-Induced Subjective Effects and Cue-Induced Craving

Newton

Roache

Garza

et al. 2005

Neuropsychopharmacol

141

126

View full text Add to dashboard Cite

show abstract

“…It is intriguing that VMAT2 mRNA and tetrabenazine binding are decreased also in limbic areas of the Flinders rat (Schwartz et al, 2003) and this animal shows many of the same endophenotypes as the Vmat2 HET mice. Previous investigations have shown that VMAT2 expression and/or its subcellular distributions are modulated by estrogen, stress, monoamine oxidase inhibitors, lithium, psychostimulants, and bupropion (Rehavi et al, 1998;Rusnák et al, 2001;Zucker et al, 2001Zucker et al, , 2005Riddle et al, 2002;Rau et al, 2005). In contrast, chronic reserpine or paroxetine treatments exert no effects on VMAT2 expression, at least in brain regions that contain 5-HT neurons (Vilpoux et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

Vmat2Heterozygous Mutant Mice Display a Depressive-Like Phenotype

Fukui¹,

Rodriguiz²,

Zhou³

et al. 2007

J. Neurosci.

136

144

View full text Add to dashboard Cite

The vesicular monoamine transporter 2 (VMAT2) is localized primarily within the CNS and is responsible for transporting monoamines from the cytoplasm into secretory vesicles. Because reserpine (a VMAT inhibitor) can precipitate depressive-like symptoms in humans, we investigated whether Vmat2 heterozygous (HET) mice present with depressive-like behaviors. The mutants showed locomotor and rearing retardation in the open field and appeared anhedonic to 1 and 1.5% sucrose solutions. Immobility times for Vmat2 heterozygotes were prolonged in forced swim and imipramine normalized this behavior. HET animals also showed enhanced immobility in tail suspension and this response was alleviated by fluoxetine, reboxetine, and bupropion. Stimulated GTP␥S binding indicated that ␣ 2 -adrenergic receptors in HET hippocampus were more sensitive to UK 14,304 (5-bromo-N-(4,5-dihydro-1-H-imidazol-2-yl)-6-quinoxalinamine) stimulation than in wild type (WT) mice. In learned helplessness, mice were exposed to a shuttle box for 4 d or were given inescapable foot-shocks for the same time period. On day 5, all animals were tested in shock escape. Failure rates and the latency to escape were similar for WT and HET mice that were only pre-exposed to the test apparatus. In foot-shock groups, learned helplessness was more robust in heterozygotes than in WT controls. Basal secretion of serum corticosterone was not distinguished by genotype; however, corticosterone levels in mutants were more responsive to stress. Anxiety-like responses of WT and HET animals in the open field, light-dark exploration, zero maze, and novelty-suppressed feeding tests were indistinguishable. Collectively, these findings suggest that Vmat2 heterozygotes display a depressive-like phenotype that is devoid of anxiety-like behavior.

show abstract

“…Chronic highdose MA exposure is thought to produce these neurotoxic effects by impairing the ability of synaptic vesicles to take up DA via disruption of the vesicular proton gradient necessary for VMAT-2 functioning (Sulzer et al, 1995;Sulzer and Rayport, 1990), resulting in accumulation of cytoplasmic DA and the subsequent production of harmful reactive oxygen species (Cubells et al, 1994;Fleckenstein et al, 1997). DA reuptake blockers such as bupropion increase vesicular dopamine uptake via enhancement of VMAT-2 function (Brown et al, 2001;Rau et al, 2005) suggesting that treatment with bupropion may counteract the MA-induced accumulation of cytosolic DA and reactive oxygen species thereby reducing the neurotoxic effects of MA. Yet, while preclinical studies have shown that treatment with the reuptake blockers methylphenidate and bupropion reversed MAinduced reductions in VMAT-2 activity, bupropion did not prevent the long-term deficits in dopaminergic function produced by repeated high-dose MA administration (Rau et al, 2005;Sandoval et al, 2003), which may explain the lack of clinical effect for bupropion among heavy-MA users.…”

Section: Discussionmentioning

confidence: 99%

“…DA reuptake blockers such as bupropion increase vesicular dopamine uptake via enhancement of VMAT-2 function (Brown et al, 2001;Rau et al, 2005) suggesting that treatment with bupropion may counteract the MA-induced accumulation of cytosolic DA and reactive oxygen species thereby reducing the neurotoxic effects of MA. Yet, while preclinical studies have shown that treatment with the reuptake blockers methylphenidate and bupropion reversed MAinduced reductions in VMAT-2 activity, bupropion did not prevent the long-term deficits in dopaminergic function produced by repeated high-dose MA administration (Rau et al, 2005;Sandoval et al, 2003), which may explain the lack of clinical effect for bupropion among heavy-MA users. Alternatively, bupropion's relatively weak effect in blocking DA reuptake (Argyelan et al, 2005;Meyer et al, 2002) may simply be overwhelmed by chronic highdose MA use.…”

Section: Discussionmentioning

confidence: 99%

“…Bupropion has relatively few antidepressant-associated side effects, such as sexual dysfunction and sedation (Stahl et al, 2004), has a low abuse potential (Nomikos et al, 1989), and is not fatal when taken in large doses (Shepherd et al, 2004). While bupropion's precise mechanism of action is not known, bupropion binds to DAT and has been shown to increase DA transmission in both the nucleus accumbens and the prefrontal cortex (Rau et al, 2005). By restoring depleted levels of monoamines, bupropion may be effective in ameliorating withdrawal symptoms and cognitive deficits in patients recovering from MA abuse, thereby reducing MA use.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Randomized, placebo-controlled trial of bupropion for the treatment of methamphetamine dependence

Shoptaw

Heinzerling

Rotheram-Fuller

et al. 2008

Drug and Alcohol Dependence

138

129

View full text Add to dashboard Cite

Objective-To compare bupropion to placebo for reducing methamphetamine (MA) use, increasing retention, and reducing the severity of depressive symptoms and MA cravings. A secondary objective compared bupropion to placebo for reducing cigarette smoking among MA dependent participants.Methods-Following a 2-week, non-medication baseline screening period, 73 treatment-seeking MA dependent participants were randomly assigned to bupropion sustained release (150 mg twice daily; N=36) or placebo (twice daily; N=37) for 12-weeks under double blind conditions. Participants attended clinic thrice weekly to provide urine samples analyzed for MA-metabolite, to complete research measures and assessments, and to receive contingency management and weekly cognitive behavioral therapy sessions.Results-There were no statistically significant effects for bupropion relative to placebo on MA use verified by urine drug screens, for reducing the severity of depressive symptoms or MA cravings, or on study retention. In a post hoc analysis, there was a statistically significant effect of bupropion treatment on MA use among participants with lighter (0-2 MA-positive urines), but not heavier (3-6 MA-positive urines) MA use during baseline (OR=2.81, 95% CI=1.61-4.93, p<0.001 for MA-free week with bupropion among light users). Bupropion treatment was also associated with significantly reduced cigarette smoking, by almost 5 cigarettes per day (p=0.0002).Conclusion-Bupropion was no more effective than placebo in reducing MA use in planned analyses, though bupropion did reduce cigarette smoking. Post hoc findings of an effect for bupropion among baseline light, but not heavy, MA users suggests further evaluation of bupropion for light MA users is warranted.

show abstract

Bupropion increases striatal vesicular monoamine transport

Cited by 65 publications

References 44 publications

Bupropion Reduces Methamphetamine-Induced Subjective Effects and Cue-Induced Craving

Bupropion Reduces Methamphetamine-Induced Subjective Effects and Cue-Induced Craving

Vmat2Heterozygous Mutant Mice Display a Depressive-Like Phenotype

Randomized, placebo-controlled trial of bupropion for the treatment of methamphetamine dependence

Contact Info

Product

Resources

About