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Neuropsychopharmacology. 2015 Mar 13;40(5):1269-77. doi: 10.1038/npp.2014.314.

Individual variation in the motivational and neurobiological effects of an opioid cue.

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Department of Psychology (Biopsychology Program), University of Michigan, Ann Arbor, MI, USA.
1] Department of Psychology (Biopsychology Program), University of Michigan, Ann Arbor, MI, USA [2] Department of Psychiatry, University of Michigan, Ann Arbor, MI, USA [3] Molecular and Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, MI, USA.


A discrete cue associated with intravenous injections of cocaine acquires greater control over motivated behavior in some rats ('sign-trackers', STs) than others ('goal-trackers', GTs). It is not known, however, if such variation generalizes to cues associated with other drugs. We asked, therefore, whether a discrete cue (a light) associated with the intravenous administration of an opioid drug (the short-acting mu receptor agonist, remifentanil) acquires incentive motivational properties differently in STs and GTs, as indicated by tests of Pavlovian conditioned approach and conditioned reinforcement. Consistent with studies using cocaine, STs approached a classically conditioned opioid cue more readily than GTs, and in a test of conditioned reinforcement worked more avidly to get it. Interestingly, STs and GTs did not differ in the acquisition of a conditioned orienting response. In addition, the performance of conditioned approach behavior, but not conditioned orientation, was attenuated by pretreatment with the dopamine receptor antagonist, flupenthixol, into the core of the nucleus accumbens. Lastly, food and opioid cues engaged similar amygdalo-striatal-thalamic circuitry to a much greater extent in STs than GTs, as indicated by Fos expression. Taken together, these data demonstrate that, similar to food and cocaine cues: (1) a discrete opioid cue attains greater incentive motivational value in STs than GTs; (2) the attribution of incentive motivational properties to an opioid cue is dopamine dependent; and (3) an opioid cue engages the so-called 'motive circuit' only if it is imbued with incentive salience.

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