Acute effects of bupropion on extracellular dopamine concentrations in rat striatum and nucleus accumbens studied by in vivo microdialysis

Nomikos, G G; Damsma, G.; Wenkstern, Danielle; Fibiger, H.C.

doi:10.1016/0893-133x(89)90031-6

Cited by 127 publications

(106 citation statements)

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“…It has been established in vitro and in vivo that BUP inhibits both the DA and NE transporters (Nomikos et al, 1989;Ferris and Cooper, 1993;Wellman, 2005). We previously demonstrated that coadministration of selective DA + NE reuptake inhibitors produces similar effects on food intake and body weight as BUP (Billes and Cowley, 2007).…”

Section: Discussionmentioning

confidence: 97%

Catecholamine Reuptake Inhibition Causes Weight Loss by Increasing Locomotor Activity and Thermogenesis

Billes

Cowley

2007

Neuropsychopharmacol

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Bupropion (BUP) is a dopamine (DA) and norepinephrine (NE) reuptake inhibitor that causes mild weight loss in obese adults. Subchronic (7 day) coadministration of selective DA and NE reuptake inhibitors also causes weight loss in mice. Because weight loss was not associated with decreased caloric intake, subchronic BUP might cause weight loss through increased energy expenditure. Acute studies demonstrate that BUP or DA + NE reuptake inhibitors cause transient hypophagia and increased locomotion; though the effects on temperature are inconsistent. Because subchronic DA + NE reuptake inhibition does not affect appetite, there is clearly a difference between the acute and subchronic effects of DA + NE reuptake inhibitors; however the effects of chronic (or subchronic) BUP on energy balance have never been directly studied in an animal model. Therefore, the acute and subchronic effects of BUP or selective DA and NE reuptake inhibitors on food intake, body weight, locomotor activity, and interscapular temperature were determined in mice. Generally, selective inhibition of DA reuptake (by GBR12783) increased activity while selective inhibition of NE reuptake (by nisoxetine, NIS) decreased activity and temperature. BUP increased activity and temperature but subchronic BUP did not significantly reduce body weight due to a compensatory increase in food intake. Subchronic DA + NE reuptake inhibitor coadministration mimicked the effect of BUP on activity and temperature, but caused weight loss because daily food intake was not increased. The results of this study suggest that the mild weight loss effect of BUP in humans may be due to increased locomotion or heat production. More importantly, inhibition of DA + NE reuptake (with GBR + NIS) increased energy expenditure without a compensatory increase in food intake, supporting a role for novel combination catecholamine reuptake inhibitors in pharmacotherapy for obesity.

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Section: Discussionmentioning

confidence: 97%

Catecholamine Reuptake Inhibition Causes Weight Loss by Increasing Locomotor Activity and Thermogenesis

Billes

Cowley

2007

Neuropsychopharmacol

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“…Among its many reported properties, bupropion inhibits pre-synaptic reuptake of norepinephrine (NE) (Cooper et al, 1994;Horst and Preskorn, 1998) and dopamine (DA) (Horst and Preskorn, 1998;Nomikos et al, 1989;Meyer et al, 2002), and increases NE release (Dong and Blier, 2001). The effect of bupropion is greater on NE reuptake and inhibition of NE cell firing than on these mechanisms within the DA system (Cooper et al, 1994;Dong and Blier, 2001;Meyer et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

Attenuation of cue-induced cigarette craving and anterior cingulate cortex activation in bupropion-treated smokers: a preliminary study

Brody

Mandelkern

Lee³

et al. 2004

Psychiatry Research: Neuroimaging

138

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In untreated smokers, exposure to cigarette-related cues increases both the intensity of cigarette craving and relative glucose metabolism of the perigenual/ventral anterior cingulate cortex (ACC). Given that treatment with bupropion HCl reduces overall cigarette craving levels in nicotine dependent subjects, we performed a preliminary study of smokers to determine if bupropion HCl treatment attenuates cue-induced cigarette craving and associated brain metabolic activation. Thirtyseven, otherwise healthy smokers (20 untreated and 17 who had received open-label treatment with bupropion HCl) underwent two 18 F-fluorodeoxyglucose positron emission tomography scanning sessions in randomized order-one when presented with neutral cues and the other when presented with cigarette-related cues. Bupropion-treated smokers had smaller cigarette cue-induced increases in craving scores on the Urge to Smoke (UTS) Scale and less activation of perigenual/ventral ACC metabolism from the neutral to the cigarette cue scan than untreated smokers. Thus, in addition to its known effects on spontaneous cigarette craving and withdrawal symptoms, bupropion HCl diminishes cue-induced cigarette craving and appears to attenuate cigarette cue-induced ACC activation. These results are consistent with the known effects of bupropion HCl, including its enhancement of catecholaminergic neurotransmission.

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“…For example, bupropion was given acutely and immediately before testing in this study, whereas in humans, its use began before quitting and continued across withdrawal period and other interventions. Regarding mechanisms of the actions of bupropion, previous research indicates that bupropion functions as an inhibitor of dopamine and norepinephrine transporters and thereby increases activity of these neurotransmitter systems (Nomikos et al 1989;Li et al 2002). Recently, bupropion was found to increase responding for a sensory reinforcer, and this effect was blocked by an α-adrenergic antagonist (prazosin) but not by the nicotinic antagonist mecamylamine (Mays et al 2007).…”

Section: Discussionmentioning

confidence: 99%

“…It has been proposed that this agent acts by blocking nicotinic acetylcholine receptors and inhibiting dopamine and norepinephrine reuptake (Nomikos et al 1989;Fryer and Lukas 1999;Slemmer et al 2000;Li et al 2002). Bupropion has been reported to alleviate nicotine withdrawal symptoms in both humans and animals (Shiffman et al 2000;Cryan et al 2003;Malin et al 2006), whereas it has had inconsistent effects on nicotine self-administration in animals Rauhut et al 2003;Shoaib et al 2003).…”

Section: Introductionmentioning

confidence: 99%

Cue-induced reinstatement of nicotine-seeking behavior in rats: effect of bupropion, persistence over repeated tests, and its dependence on training dose

et al. 2007

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Rationale-The motivational effects of nicotine-associated cues have been demonstrated in animal studies. However, it is unknown whether the effectiveness of nicotine cues in reinstating nicotineseeking varies with the extent of prior nicotine self-administration. In addition, the issue of whether bupropion (an FDA-approved smoking cessation medication) interferes with the conditioned incentive of nicotine cues remains to be addressed.Objective-This study determined the relationship of cue-reinstated nicotine-seeking and the levels of prior self-administration and examined the effect of bupropion on cue-induced reinstatement of nicotine-seeking in comparison with that on self-administration. Materials and methods-MaleSprague-Dawley rats were trained in daily 1-h sessions to intravenously self-administer nicotine at different doses (0, 0.015, 0.03, 0.06 mg/kg/infusion) and to associate an auditory/visual cue with each nicotine delivery. After extinction, three reinstatement tests at 15 day intervals were conducted with re-presentation of the cue without nicotine delivery. In separate groups of rats trained with 0.03 mg/kg/infusion nicotine, bupropion (0, 10, 20, 40 mg/kg) was intraperitoneally administered to different groups before the reinstatement and in a withinsubject design before the self-administration tests.Results-Cue-induced reinstatement of active lever responses was observed at all nicotine doses in the first reinstatement test, but at only the two highest doses during the second and third tests. The magnitude of reinstatement was positively correlated with level of prior responding for nicotine. Bupropion pretreatment decreased nicotine self-administration but enhanced cue-reinstated nicotineseeking.Conclusions-These results demonstrate the positive correlation of cue-reinstated nicotineseeking with prior responding for nicotine self-administration and the persistence of the cue effect after taking higher doses of nicotine. The results of pharmacological tests suggest that although it is able to help achieve smoking cessation, bupropion may have little clinical benefit for the prevention of relapse associated with exposure to environmental smoking cues.

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Acute effects of bupropion on extracellular dopamine concentrations in rat striatum and nucleus accumbens studied by in vivo microdialysis

Cited by 127 publications

References 0 publications

Catecholamine Reuptake Inhibition Causes Weight Loss by Increasing Locomotor Activity and Thermogenesis

Catecholamine Reuptake Inhibition Causes Weight Loss by Increasing Locomotor Activity and Thermogenesis

Attenuation of cue-induced cigarette craving and anterior cingulate cortex activation in bupropion-treated smokers: a preliminary study

Cue-induced reinstatement of nicotine-seeking behavior in rats: effect of bupropion, persistence over repeated tests, and its dependence on training dose

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