Nicotine-Induced Dopamine Release in Primates Measured with [11C]Raclopride PET

Marenco, Stefano; Carson, Richard E.; Berman, Karen F.; Herscovitch, Peter; Weinberger, Daniel R.

doi:10.1038/sj.npp.1300287

Cited by 59 publications

(52 citation statements)

References 61 publications

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“…Addiction to tobacco is thought to involve the effects of nicotine, its main addictive component (Stolerman et al, 1995), on the dopaminergic system (Balfour et al, 2000;Pidoplichko et al, 1997) as nicotinic receptors have been identified on nigrostriatal and mesolimbic dopaminergic neurons (Clarke and Pert, 1985). Supporting this, studies in rodents and non-human primates show that tobacco or nicotine increase dopamine neuron firing (Grenhoff et al, 1986;Zhang and Sulzer, 2004), increase dopamine release (Dewey et al, 1999;Gallezot et al, 2013;Marenco et al, 2004;Pontieri et al, 1996), and increase dopamine synthesis (Tsukada et al, 2005) in the striatum.…”

Section: Introductionmentioning

confidence: 73%

Dopamine Function in Cigarette Smokers: An [18F]-DOPA PET Study

Bloomfield

Pepper

Egerton

et al. 2014

Neuropsychopharmacol

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Tobacco addiction is a global public health problem. Addiction to tobacco is thought to involve the effects of nicotine on the dopaminergic system. Only one study has previously investigated dopamine synthesis capacity in cigarette smokers. This study, exclusively in male volunteers, reported increased dopamine synthesis capacity in heavy smokers compared with non-smokers. We sought to determine whether dopamine synthesis capacity was elevated in a larger sample of cigarette smokers that included females. Dopamine synthesis capacity was measured in 15 daily moderate smokers with 15 sex-and age-matched control subjects who had never smoked tobacco. Dopamine synthesis capacity (indexed as the influx rate constant K i cer ) was measured with positron emission tomography and 3,4-dihydroxy-6-[ 18 F]-fluoro-l-phenylalanine. There was no significant group difference in dopamine synthesis capacity between smokers and non-smoker controls in the whole striatum (t 28 ¼ 0.64, p ¼ 0.53) or any of its functional subdivisions. In smokers, there were no significant relationships between the number of cigarettes smoked per day and dopamine synthesis capacity in the whole striatum (r ¼ À 0.23, p ¼ 0.41) or any striatal subdivision. These findings indicate that moderate smoking is not associated with altered striatal dopamine synthesis capacity.

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Section: Introductionmentioning

confidence: 73%

Dopamine Function in Cigarette Smokers: An [18F]-DOPA PET Study

Bloomfield

Pepper

Egerton

et al. 2014

Neuropsychopharmacol

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“…Striatal DA release in response to a nicotine or cigarette challenge has been demonstrated repeatedly in both non-human primates and humans (Brody et al, 2004a;Dewey et al, 1999;Marenco et al, 2004;Tsukada et al, 2002), with the majority of these studies using PET and the radiotracer 11 C-raclopride (a relatively specific D 2 receptor binder) to demonstrate DA release through radiotracer displacement. These studies have reported a wide range of DA concentration change.…”

Section: Brain Dopamine Responses To Nicotine and Smokingmentioning

confidence: 99%

“…These studies have reported a wide range of DA concentration change. In two studies that examined the question directly (Marenco et al, 2004;Tsukada et al, 2002), nicotine was found to result in less radiotracer displacement than amphetamine, while it has also been reported that nicotine-induced DA release is comparable in magnitude to that induced by other addictive drugs (Pontieri et al, 1996). In addition, an association between 11 C-raclopride displacement and the hedonic effects of smoking (defined as elation and euphoria) has been demonstrated (Barrett et al, 2004), though this study did not find an overall difference between the smoking and non-smoking conditions.…”

Section: Brain Dopamine Responses To Nicotine and Smokingmentioning

confidence: 99%

Functional brain imaging of tobacco use and dependence

Brody

2006

Journal of Psychiatric Research

176

136

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While most cigarette smokers endorse a desire to quit smoking, only about 14% to 49% will achieve abstinence after 6 months or more of treatment. A greater understanding of the effects of smoking on brain function may (in conjunction with other lines of research) result in improved pharmacological (and behavioral) interventions. Many research groups have examined the effects of acute and chronic nicotine/cigarette exposure on brain activity using functional imaging; the purpose of this paper is to synthesize findings from such studies and present a coherent model of brain function in smokers. Responses to acute administration of nicotine/smoking include: a reduction in global brain activity; activation of the prefrontal cortex, thalamus, and visual system; activation of the thalamus and visual cortex during visual cognitive tasks; and increased dopamine (DA) concentration in the ventral striatum/nucleus accumbens. Responses to chronic nicotine/cigarette exposure include decreased monoamine oxidase (MAO) A and B activity in the basal ganglia and a reduction in α 4 β 2 nicotinic acetylcholine receptor (nAChR) availability in the thalamus and putamen. Taken together, these findings indicate that smoking enhances neurotransmission through cortico-basal ganglia-thalamic circuits either by direct stimulation of nAChRs, indirect stimulation via DA release or MAO inhibition, or a combination of these factors. Activation of this circuitry may be responsible for the effects of smoking seen in tobacco dependent subjects, such as improvements in attentional performance, mood, anxiety, and irritability.

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“…Unlike those psychostimulants, nicotine is known to produce relatively weak elevation in DA levels (Forget et al, 2010;Pontieri et al, 1996), which may explain why initial PET studies in animals report small, inconsistent changes in response to intravenous nicotine (Cumming et al, 2003;Marenco et al, 2004;Tsukada et al, 2002). Subsequently, in some studies smoking nicotine-containing cigarettes produced modest changes in [ 11 C]-raclopride binding in the limbic striatum (Brody et al, 2009;Brody et al, 2006;Brody et al, 2004;Domino et al, 2012;Domino et al, 2013) or in others, changes in [ 11 C]-raclopride binding were limited to those smokers finding the experience of nicotine/smoking pleasurable (Barrett et al, 2004;Montgomery et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Elevation of Dopamine Induced by Cigarette Smoking: Novel Insights from a [11C]-(+)-PHNO PET Study in Humans

Foll

Guranda

Wilson

et al. 2013

Neuropsychopharmacol

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Positron emission tomography (PET) has convincingly provided in vivo evidence that psychoactive drugs increase dopamine (DA) levels in human brain, a feature thought critical to their reinforcing properties. Some controversy still exists concerning the role of DA in reinforcing smoking behavior and no study has explored whether smoking increases DA concentrations at the D3 receptor, speculated to have a role in nicotine's addictive potential. Here, we used PET and]oxazin-9-ol) to test the hypothesis that smoking increases DA release (decreases [ 11 C]-( þ )-PHNO binding) in D2-rich striatum and D3-rich extra-striatal regions and is related to craving, withdrawal and smoking behavior. Ten participants underwent [ 11 C]-( þ )-PHNO scans after overnight abstinence and after smoking a cigarette. Motivation to smoke (smoking topography), mood, and craving were recorded. Smoking significantly decreased self-reported craving, withdrawal, and [ 11 C]-( þ )-PHNO binding in D2 and D3-rich areas ( À 12.0 and À 15.3%, respectively). We found that motivation to smoke (puff rate) predicted magnitude of DA release in limbic striatum, and the latter was correlated with decreased craving and withdrawal symptoms. This is the first report suggesting that, in humans, DA release is increased in D3-rich areas in response to smoking. Results also support the preferential involvement of the limbic striatum in motivation to smoke, anticipation of pleasure from cigarettes and relief of withdrawal symptoms. We propose that due to the robust effect of smoking on [ 11 C]-( þ )-PHNO binding, this radiotracer represents an ideal translational tool to investigate novel therapeutic strategies targeting DA transmission.

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Nicotine-Induced Dopamine Release in Primates Measured with [11C]Raclopride PET

Cited by 59 publications

References 61 publications

Dopamine Function in Cigarette Smokers: An [18F]-DOPA PET Study

Dopamine Function in Cigarette Smokers: An [18F]-DOPA PET Study

Functional brain imaging of tobacco use and dependence

Elevation of Dopamine Induced by Cigarette Smoking: Novel Insights from a [11C]-(+)-PHNO PET Study in Humans

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