Impulsive Choice and Impulsive Action Predict Vulnerability to Distinct Stages of Nicotine Seeking in Rats

Published:September 20, 2007DOI:


      Although heavy smoking has been associated with impulsivity in humans, it is not clear whether poor impulse control represents a risk factor in the etiology of nicotine dependence.


      To address this issue, rats were selected on the basis of individual differences in impulsivity in the delayed reward task (impulsive choice) and the 5-choice serial reaction time task (impulsive action). Subsequently, rats were subjected to a nicotine self-administration (SA) paradigm tailored to measure the motivational properties of nicotine and nicotine-associated stimuli. In separate groups, differences in electrically evoked dopamine release in slice preparations obtained from several mesolimbic brain regions were determined.


      Impulsive action was associated with an enhanced motivation to initiate and maintain nicotine SA. In contrast, impulsive choice predicted a diminished ability to inhibit nicotine seeking during abstinence and an enhanced vulnerability to relapse upon re-exposure to nicotine cues. Impulsive action was associated with reduced dopamine release in the accumbens core and impulsive choice with reduced dopamine release in accumbens core, shell, and medial prefrontal cortex.


      The strong association between sub-dimensions of impulsivity and nicotine SA implies that interventions aimed to improve impulse control might help to reduce susceptibility to nicotine dependence and/or lead to successful smoking cessation.

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        • Evenden J.L.
        Varieties of impulsivity.
        Psychopharmacology. 1999; 146: 348-361
        • Winstanley C.A.
        • Eagle D.M.
        • Robbins T.W.
        Behavioral models of impulsivity in relation to ADHD: Translation between clinical and preclinical studies.
        Clin Psychol Rev. 2006; 26: 379-395
        • Bickel W.K.
        • Odum A.L.
        • Madden G.J.
        Impulsivity and cigarette smoking: Delay discounting in current, never, and ex-smokers.
        Psychopharmacology (Berl). 1999; 146: 447-454
        • Mitchell S.H.
        Measures of impulsivity in cigarette smokers and non-smokers.
        Psychopharmacology (Berl). 1999; 146: 455-464
        • Spinella M.
        Correlations between orbitofrontal dysfunction and tobacco smoking.
        Addict Biol. 2002; 7: 381-384
        • Skinner M.D.
        • Aubin H.J.
        • Berlin I.
        Impulsivity in smoking, nonsmoking, and ex-smoking alcoholics.
        Addict Behav. 2004; 29: 973-978
        • Robbins T.W.
        The 5-choice serial reaction time task: Behavioural pharmacology and functional neurochemistry.
        Psychopharmacology. 2002; 163: 362-380
        • Evenden J.L.
        • Ryan C.N.
        The pharmacology of impulsive behaviour in rats: The effects of drugs on response choice with varying delays of reinforcement.
        Psychopharmacology (Berl). 1996; 128: 161-170
        • Perry J.L.
        • Larson E.B.
        • German J.P.
        • Madden G.J.
        • Carroll M.E.
        Impulsivity (delay discounting) as a predictor of acquisition of IV cocaine self-administration in female rats.
        Psychopharmacology. 2005; 178: 193-201
        • Dalley J.W.
        • Fryer T.D.
        • Brichard L.
        • Robinson E.S.J.
        • Theobald D.E.
        • Laane K.
        • et al.
        Nucleus accumbens D2/3 receptors predict trait impulsivity and cocaine reinforcement.
        Science. 2007; 315: 1267-1270
        • Le Foll B.
        • Goldberg S.R.
        Control of the reinforcing effects of nicotine by associated environmental stimuli in animals and humans.
        Trends Pharmacol Sci. 2005; 26: 287-293
        • De Vries T.J.
        • Schoffelmeer A.N.M.
        Cannabinoid CB1 receptors control conditioned drug seeking.
        Trends Pharmacol Sci. 2005; 26: 420-426
        • Chiamulera C.
        Cue reactivity in nicotine and tobacco dependence: A “multiple-action” model of nicotine as a primary reinforcement and as an enhancer of the effects of smoking-associated stimuli.
        Brain Res Rev. 2005; 48: 74-97
        • Bechara A.
        • Tranel D.
        • Damasio H.
        Characterization of the decision-making deficit of patients with ventromedial prefrontal cortex lesions.
        Brain. 2000; 123: 2189-2202
        • Cardinal R.N.
        • Pennicott D.R.
        • Sugathapala C.L.
        • Robbins T.W.
        • Everitt B.J.
        Impulsive choice induced in rats by lesions of the nucleus accumbens core.
        Science. 2001; 292: 2499-2501
        • Christakou A.
        • Robbins T.W.
        • Everitt B.J.
        Prefrontal cortical-ventral striatal interactions involved in affective modulation of attentional performance: Implications for corticostriatal circuit function.
        J Neurosci. 2004; 24: 773-780
        • Cole B.J.
        • Robbins T.W.
        Amphetamine impairs the discriminative performance of rats with dorsal noradrenergic bundle lesions on a 5-choice serial reaction time task: New evidence for central dopaminergic-noradrenergic interactions.
        Psychopharmacology (Berl). 1987; 91: 458-466
        • Pattij T.
        • Janssen M.C.
        • Vanderschuren L.J.
        • Schoffelmeer A.N.
        • van Gaalen M.M.
        Involvement of dopamine D(1) and D (2) receptors in the nucleus accumbens core and shell in inhibitory response control.
        Psychopharmacology (Berl). 2006; 191: 587-598
        • Stein E.A.
        • Pankiewicz J.
        • Harsch H.H.
        • Cho J.K.
        • Fuller S.A.
        • Hoffmann R.G.
        • et al.
        Nicotine-induced limbic cortical activation in the human brain: A functional MRI study.
        Am J Psychiatry. 1998; 155: 1009-1015
        • Shaham Y.
        • Shalev U.
        • Lu L.
        • de Wit H.
        • Stewart J.
        The reinstatement model of drug relapse: History, methodology and major findings.
        Psychopharmacology. 2003; 168: 3-20
        • De Vries T.J.
        • Shaham Y.
        • Homberg J.R.
        • Crombag H.
        • Schuurman K.
        • Dieben J.
        • et al.
        A cannabinoid mechanism in relapse to cocaine seeking.
        Nat Med. 2001; 7: 1151-1154
        • Kalivas P.W.
        • McFarland K.
        Brain circuitry and the reinstatement of cocaine-seeking behavior.
        Psychopharmacology. 2003; 168: 44-56
        • Schmidt E.D.
        • Voorn P.
        • Binnekade R.
        • Schoffelmeer A.N.M.
        • de Vries T.J.
        Differential involvement of the prelimbic cortex and striatum in conditioned heroin and sucrose seeking following long-term extinction.
        Eur J Neurosci. 2005; 22: 2347-2356
        • Naqvi N.H.
        • Rudrauf D.
        • Damasio H.
        • Bechara A.
        Damage to the insula disrupts addiction to cigarette smoking.
        Science. 2007; 315: 531-534
        • Jentsch J.D.
        • Taylor J.R.
        Impulsivity resulting from frontostriatal dysfunction in drug abuse: Implications for the control of behavior by reward-related stimuli.
        Psychopharmacology. 1999; 146: 373-390
        • van Gaalen M.M.
        • Brueggeman R.J.
        • Bronius P.F.
        • Schoffelmeer A.N.
        • Vanderschuren L.J.
        Behavioral disinhibition requires dopamine receptor activation.
        Psychopharmacology (Berl). 2006; 187: 73-85
        • van Gaalen M.M.
        • van Koten R.
        • Schoffelmeer A.N.M.
        • Vanderschuren L.J.M.J.
        Critical involvement of dopaminergic neurotransmission in impulsive decision making.
        Biological Psychiatry. 2006; 60: 66-73
        • De Vries T.J.
        • de Vries W.
        • Janssen M.C.W.
        • Schoffelmeer A.N.M.
        Suppression of conditioned nicotine and sucrose seeking by the cannabinoid-1 receptor antagonist SR141716A.
        Behav Brain Res. 2005; 161: 164-168
        • Schoffelmeer A.N.
        • Rice K.C.
        • Jacobson A.E.
        • Van Gelderen J.G.
        • Hogenboom F.
        • Heijna M.H.
        • et al.
        Mu-, delta- and kappa-opioid receptor-mediated inhibition of neurotransmitter release and adenylate cyclase activity in rat brain slices: Studies with fentanyl isothiocyanate.
        Eur J Pharmacol. 1988; 154: 169-178
        • Donny E.C.
        • Caggiula A.R.
        • Mielke M.M.
        • Booth S.
        • Gharib M.A.
        • Hoffman A.
        • et al.
        Nicotine self-administration in rats on a progressive ratio schedule of reinforcement.
        Psychopharmacology. 1999; 147: 135-142
        • Markou A.
        • Weiss F.
        • Gold L.H.
        • Caine S.B.
        • Schulteis G.
        • Koob G.F.
        Animal models of drug craving.
        Psychopharmacology (Berl). 1993; 112: 163-182
        • Poulos C.X.
        • Le A.D.
        • Parker J.L.
        Impulsivity predicts individual susceptibility to high levels of alcohol self-administration.
        Behav Pharmacol. 1995; 6: 810-814
        • Mitchell S.H.
        Measuring impulsivity and modeling its association with cigarette smoking.
        Behav Cogn Neurosci Rev. 2004; 3: 261-275
        • Bowden-Jones H.
        • McPhillips M.
        • Rogers R.
        • Hutton S.
        • Joyce E.
        Risk-taking on tests sensitive to ventromedial prefrontal cortex dysfunction predicts early relapse in alcohol dependency: A pilot study.
        J Neuropsychiatry Clin Neurosci. 2005; 17: 417-420
        • Paulus M.P.
        • Tapert S.F.
        • Schuckit M.A.
        Neural activation patterns of methamphetamine-dependent subjects during decision making predict relapse.
        Arch Gen Psych. 2005; 62: 761-768
        • Blondeau C.
        • Dellu-Hagedorn F.
        Dimensional analysis of ADHD subtypes in rats.
        Biol Psychiatry. 2007; 61: 1340-1350
        • Cole B.J.
        • Robbins T.W.
        Effects of 6-hydroxydopamine lesions of the nucleus accumbens septi on performance of a 5-choice serial reaction time task in rats: Implications for theories of selective attention and arousal.
        Behav Brain Res. 1989; 33: 165-179
        • Dalley J.W.
        • Theobald D.E.
        • Pereira E.A.
        • Li P.M.
        • Robbins T.W.
        Specific abnormalities in serotonin release in the prefrontal cortex of isolation-reared rats measured during behavioural performance of a task assessing visuospatial attention and impulsivity.
        Psychopharmacology (Berl). 2002; 164: 329-340
        • de Wit H.
        • Enggasser J.L.
        • Richards J.B.
        Acute administration of d-amphetamine decreases impulsivity in healthy volunteers.
        Neuropsychopharmacol. 2002; 27: 813-825
        • Manes F.
        • Sahakian B.
        • Clark L.
        • Rogers R.
        • Antoun N.
        • Aitken M.
        • et al.
        Decision-making processes following damage to the prefrontal cortex.
        Brain. 2002; 125: 624-639
        • Corrigall W.A.
        • Franklin K.B.
        • Coen K.M.
        • Clarke P.B.
        The mesolimbic dopaminergic system is implicated in the reinforcing effects of nicotine.
        Psychopharmacology (Berl). 1992; 107: 285-289
        • Corrigall W.A.
        • Coen K.M.
        • Adamson K.L.
        Self-administered nicotine activates the mesolimbic dopamine system through the ventral tegmental area.
        Brain Res. 1994; 653: 278-284
        • Brody A.L.
        Functional brain imaging of tobacco use and dependence.
        J Psychiatr Res. 2005; 40: 404-418
        • Lecca D.
        • Cacciapaglia F.
        • Valentini V.
        • Gronli J.
        • Spiga S.
        • Di Chiara G.
        Preferential increase of extracellular dopamine in the rat nucleus accumbens shell as compared to that in the core during acquisition and maintenance of intravenous nicotine self-administration.
        Psychopharmacology. 2006; 184: 435-446
        • Pontieri F.E.
        • Tanda G.
        • Orzi F.
        • DiChiara G.
        Effects of nicotine on the nucleus accumbens and similarity to those of addictive drugs.
        Nature. 1996; 382: 255-257
        • McLaughlin J.
        • See R.E.
        Selective inactivation of the dorsomedial prefrontal cortex and the basolateral amygdala attenuates conditioned-cued reinstatement of extinguished cocaine-seeking behavior in rats.
        Psychopharmacology. 2003; 168: 57-65
        • Childress A.R.
        • Mozley P.D.
        • McElgin W.
        • Fitzgerald J.
        • Reivich M.
        • O’Brien C.P.
        Limbic activation during cue-induced cocaine craving.
        Am J Psychiatry. 1999; 156: 11-18
        • Due D.L.
        • Huettel S.A.
        • Hall W.G.
        • Rubin D.C.
        Activation in mesolimbic and visuospatial neural circuits elicited by smoking cues: Evidence from functional magnetic resonance imaging.
        Am J Psychiatry. 2002; 159: 954-960
        • Winstanley C.A.
        • Theobald D.E.
        • Dalley J.W.
        • Cardinal R.N.
        • Robbins T.W.
        Double dissociation between serotonergic and dopaminergic modulation of medial prefrontal and orbitofrontal cortex during a test of impulsive choice.
        Cereb Cortex. 2006; 16: 106-114
        • Winstanley C.A.
        • Theobald D.E.
        • Cardinal R.N.
        • Robbins T.W.
        Contrasting roles of basolateral amygdala and orbitofrontal cortex in impulsive choice.
        J Neurosci. 2004; 24: 4718-4722
        • Winstanley C.A.
        • Baunez C.
        • Theobald D.E.
        • Robbins T.W.
        Lesions to the subthalamic nucleus decrease impulsive choice but impair autoshaping in rats: The importance of the basal ganglia in Pavlovian conditioning and impulse control.
        Eur J Neurosci. 2005; 21: 3107-3116
        • Uslaner J.M.
        • Robinson T.E.
        Subthalamic nucleus lesions increase impulsive action and decrease impulsive choice—mediation by enhanced incentive motivation?.
        Eur J Neurosci. 2006; 24: 2345-2354
        • Winstanley C.A.
        • Dalley J.W.
        • Theobald D.E.H.
        • Robbins T.W.
        Fractionating impulsivity: Contrasting effects of central 5-HT depletion on different measures of impulsive behavior.
        Neuropsychopharmacol. 2004; 29: 1331-1343