Effect of a history of major depressive disorder on smoking-induced dopamine release.

Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, California 90095, USA.
Biological psychiatry (Impact Factor: 9.47). 07/2009; 66(9):898-901. DOI: 10.1016/j.biopsych.2009.06.011
Source: PubMed

ABSTRACT Dopamine (DA) system dysfunction is implicated in the pathophysiology of major depressive disorder (MDD). We sought to determine if cigarette smokers with a history of MDD and current mild depressive symptoms have abnormal smoking-induced DA release (measured indirectly as change in (11)C-raclopride binding potential [BP(ND)]).
Fifty-six cigarette smokers either with (n = 10) or without (n = 46) a history of MDD (MDD+ and MDD-, respectively) underwent bolus-plus-continuous-infusion (11)C-raclopride positron emission tomography, during which they smoked a regular cigarette. Presmoking to postsmoking changes in (11)C-raclopride BP(ND) were compared between groups. Also, correlations were determined between change in BP(ND) and depression, anxiety, and withdrawal rating scale scores for the MDD+ group.
The MDD+ group had a significantly greater reduction in (11)C-raclopride BP(ND) (-16.3%) than the MDD- group (-8.4%) (analysis of covariance [ANCOVA], p = .03). Significant negative correlations were found between depression/anxiety and change in (11)C-raclopride BP(ND) (r = -.77, p < .01 and r = -.74, p = .01, respectively).
MDD+ smokers have greater smoking-induced DA release than MDD- smokers, and higher depression/anxiety levels are associated with greater smoking-induced DA release. These findings support the theory that MDD+ smokers have DA system dysfunction, including heightened smoking-induced DA release.

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    ABSTRACT: The radiotracer [(11)C]PHNO may have advantages over other dopamine (DA) D2/D3 receptor ligands because, as an agonist, it measures high-affinity, functionally active D2/D3 receptors, whereas the traditionally used radiotracer [(11)C]raclopride measures both high- and low-affinity receptors. Our aim was to take advantage of the strength of [(11)C]PHNO for measuring the small DA signal induced by nicotine, which has been difficult to measure in preclinical and clinical neuroimaging studies. Nicotine- and amphetamine-induced DA release in non-human primates was measured with [(11)C]PHNO and [(11)C]raclopride positron emission tomography (PET) imaging. Seven adult rhesus monkeys were imaged on a FOCUS 220 PET scanner after injection of a bolus of [(11)C]PHNO or [(11)C]raclopride in three conditions: baseline; preinjection of nicotine (0.1 mg/kg bolus+0.08 mg/kg infusion over 30 min); preinjection of amphetamine (0.4 mg/kg, 5 min before radiotracer injection). DA release was measured as change in binding potential (BPND). Nicotine significantly decreased BPND in the caudate (7±8%), the nucleus accumbens (10±7%), and in the globus pallidus (13±15%) measured with [(11)C]PHNO, but did not significantly decrease BPND in the putamen or the substantia nigra or in any region when measured with [(11)C]raclopride. Amphetamine significantly reduced BPND in all regions with both radiotracers. In the striatum, larger amphetamine-induced changes were detected with [(11)C]PHNO compared with [(11)C]raclopride (52-64% vs 33-35%, respectively). We confirmed that [(11)C]PHNO is more sensitive than [(11)C]raclopride to nicotine- and amphetamine-induced DA release. [(11)C]PHNO PET may be more sensitive to measuring tobacco smoking-induced DA release in human tobacco smokers.Neuropsychopharmacology advance online publication, 13 November 2013; doi:10.1038/npp.2013.286.
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    ABSTRACT: Background There is a disproportionately high smoking prevalence among individuals who are prone to depression. While depression has been conceptualized as a disorder of dysregulated positive affect and disrupted reward processing, little research has been conducted to determine the role of smoking in these processes among depression-prone smokers. Methods Depression-prone smokers (DP+; n = 34) and smokers not depression-prone (DP-; n=49) underwent two laboratory sessions, once while smoking abstinent and once while smoking ad-libitum, to assess the relative reinforcing value of smoking and reward sensitivity. Using experience sampling methods, participants completed self-report measures of subjective reward, positive affect, and negative affect across three days while smoking as usual and three days while smoking abstinent. Results DP+ were two times more likely to work for cigarette puffs versus money in a progressive ratio, choice task (OR 2.05; CI 95% 1.04 to 4.06, p=0.039) compared to DP-. Reward sensitivity as measured by the signal detection task did not yield any significant findings. Mixed models regressions revealed a 3-way interaction (depression group, smoking phase, and time) for subjective reward, negative affect and positive affect. For all three of these outcomes, the slopes for DP- and DP+ differed significantly from each other (p’s < 0.05), and the effect of smoking (vs. abstinence) over time was greater for DP+ than DP- smokers (p’s <0.05). Conclusions These findings indicate that the effects of smoking on reward and positive affect regulation are specific to DP+ smokers and highlight novel targets for smoking cessation treatment in this population.
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