Impulsivity and chronic stress are associated with amphetamine-induced striatal dopamine release. Neuroimage

Department of Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, MD 21205, USA.
NeuroImage (Impact Factor: 6.36). 06/2007; 36(1):153-66. DOI: 10.1016/j.neuroimage.2007.01.055
Source: PubMed


A challenging question that continues to plague the field of addiction is why some individuals are more vulnerable for substance use disorders than others. Several important risk factors for substance abuse have been identified in clinical studies, including trait impulsivity and environmental stress. However, the neurobiological mechanisms that underlie the relationships remain poorly understood. The purpose of this study was to examine associations among impulsivity, stress, and striatal dopamine (DA) responses to amphetamine (AMPH) in humans. Forty healthy M, F adults, ages 18-29 years, completed self-report measures of trait impulsivity, life events stress, and perceived stress. Subjects subsequently underwent two consecutive 90-min positron emission tomography (PET) studies with high specific activity [11C]raclopride. The first scan was preceded by an intravenous injection of saline; the second was preceded by 0.3 mg/kg AMPH. Findings showed that high impulsivity was associated with blunted right ventral striatal DA release. However, effects were modified by a significant interaction with life events stress. Dopamine release was greater in low vs. high impulsivity subjects under conditions of low or moderate stress. Under conditions of high stress, both groups had low DA release. Subjects with high impulsivity reported more pleasant effects with AMPH than subjects with low impulsivity. In contrast, stress was negatively associated with pleasant drug effects. No associations were observed between impulsivity or stress and cortisol responses to AMPH. The findings are consistent with notions that blunted DA responses represent an endophenotype for substance use disorders.

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    • "Based on these results, there would be no point saying it is impulsiveness as some sort of underlying trait that correlates with BMI, and this is an important finding in its own right. The sum score of N5: Impulsiveness has been related to several other interesting outcomes, including BMI change, eating behaviours and disorders, leptin levels, white blood cell counts, drug and alcohol consumption, gambling and brain activity, such as dopamine secretion and reward responsiveness (Bagby et al., 2007; Elfhag & Morey, 2008; Jen, Saunders, Ornstein, Kamali, & McInnis, 2013; Oswald et al., 2007; Ruiz, Pincus, & Dickinson, 2003; Sutin, Costa et al., 2013; Sutin, Evans, & Zonderman, 2013; Sutin, Zonderman et al., 2013; Sutin et al., 2011, 2012; Villafuerte et al., 2012). It would be interesting to reanalyse these effects for ION to understand if these outcomes pertain to trait Impulsiveness as the underlying attribute, or something more specific (cf. "
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    ABSTRACT: In personality research, trait–outcome associations are often studied by correlating scale sum scores with an outcome. For example, an association between the NEO Impulsiveness scale and body mass index (BMI) is often interpreted to pertain to underlying trait Impulsiveness. We propose that this expectation can be corroborated by testing for Spearman's theorem of indifference of indicator. Namely, an underlying trait–outcome association should not depend on the specific items (i.e. indicators) used to measure the trait. To test this theorem, we outline an indicator exclusion procedure and demonstrate its viability using a simulation design. We then apply this procedure to test personality–BMI associations for indifference of indicator in a large population-based sample of adult Estonians (N = 2581) using self-ratings and informant ratings obtained with the NEO Personality Inventory-3. Our results show that the N5: Impulsiveness–BMI association mostly depends on two eating-related items, suggesting that the trait associated with BMI may be narrower than the trait the N5: Impulsiveness scale is supposed to measure. Associations between BMI, E3: Assertiveness and C2: Order seem to pertain to the trait. In sum, testing for indifference of indicator provides a potentially useful method to clarify trait–outcome relationships. R scripts are provided that implement the indicator exclusion procedure. Copyright © 2015 European Association of Personality Psychology
    European Journal of Personality 08/2015; DOI:10.1002/per.2009 · 3.35 Impact Factor
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    • "A relationship between the striatum and impulsivity has been reported using animal models where NAcc damage was associated with persistent impulsive behaviors, including preference for small immediate over larger delayed reinforcement (Cardinal et al., 2001). Neuroimaging studies in humans have found IMP positively related to ventral striatal (VS) BOLD reward notification using fMRI (Bjork et al., 2008) and negatively related to VS amphetamine-induced DA release using PET (Oswald et al., 2007), similar to the findings in this study. However, as other research suggests that striatal DA release is itself regulated by the PFC (Louilot et al., 1989; Deutch and Roth, 1991; Olsen and Duvauchelle, 2001; Thompson and Moss, 1995), our results may begin to probe these relationships. "
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    ABSTRACT: Impulsivity, and in particular the negative urgency aspect of this trait, is associated with poor inhibitory control when experiencing negative emotion. Individual differences in aspects of impulsivity have been correlated with striatal dopamine D2/D3 receptor availability and function. This multi-modal pilot study used both positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) to evaluate dopaminergic and neural activity, respectively, using modified versions of the monetary incentive delay task. Twelve healthy female subjects underwent both scans and completed the NEO Personality Inventory Revised to assess Impulsiveness (IMP). We examined the relationship between nucleus accumbens (NAcc) dopaminergic incentive/reward release, measured as a change in D2/D3 binding potential between neutral and incentive/reward conditions with [11C]raclopride PET, and blood oxygen level-dependent (BOLD) activation elicited during the anticipation of rewards, measured with fMRI. Left NAcc incentive/reward dopaminergic release correlated with anticipatory reward activation within the medial prefrontal cortex (mPFC), left angular gyrus, mammillary bodies, and left superior frontal cortex. Activation in the mPFC negatively correlated with IMP and mediated the relationship between IMP and incentive/reward dopaminergic release in left NAcc. The mPFC, with a regulatory role in learning and valuation, may influence dopamine incentive/reward release.
    Psychiatry Research: Neuroimaging 09/2014; 223(3). DOI:10.1016/j.pscychresns.2014.05.015 · 2.42 Impact Factor
    • "It has been suggested that dysfunctional monoaminergic signalling, particularly related to dopaminergic and noradrenergic function, contribute to impulsivity based on the therapeutic efficacy of drugs used to treat ADHD, such as the mixed dopamine (DA)/noradrenaline reuptake inhibitor methylphenidate and the noradrenaline reuptake inhibitor atomoxetine (Del Campo et al, 2011). Indeed, positron emission tomography studies have identified alterations in DA release (Buckholtz et al, 2010; Oswald et al, 2007) and the availability of DA receptors D2 and/or D3 (referred to here as D2-like receptors) in the striatum (Ghahremani et al, 2012; Lee et al, 2009) of impulsive individuals. Serotonergic (5HT) dysfunction has also been implicated, with enhanced levels of impulsivity predictive for reduced 5HT2A receptor and 5HT transporter binding in the PFC (Lindström et al., 2004; Meyer et al., 2008). "
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    ABSTRACT: Impulsivity describes the tendency of an individual to act prematurely without foresight and is associated with a number of neuropsychiatric co-morbidities, including drug addiction. As such, there is increasing interest in the neurobiological mechanisms of impulsivity, as well as the genetic and environmental influences that govern the expression of this behaviour. Tests used on rodent models of impulsivity share strong parallels with tasks used to assess this trait in humans, and studies in both suggest a crucial role of monoaminergic corticostriatal systems in the expression of this behavioural trait. Furtherore, rodent models have enabled investigation of the causal relationship between drug abuse and impulsivity. Here, we review the use of rodent models of impulsivity for investigating the mechanisms involved in this trait, and how these mechanisms could contribute to the pathogenesis of addiction.
    Disease Models and Mechanisms 01/2013; 6(2). DOI:10.1242/dmm.010934 · 4.97 Impact Factor
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