Dopamine or opioid stimulation of nucleus accumbens similarly amplify cue‐triggered ‘wanting’ for reward: entire core and medial shell mapped as substrates for PIT enhancement

Abstract

Pavlovian cues [conditioned stimulus ( CS +)] often trigger intense motivation to pursue and consume related reward [unconditioned stimulus ( UCS )]. But cues do not always trigger the same intensity of motivation. Encountering a reward cue can be more tempting on some occasions than on others. What makes the same cue trigger more intense motivation to pursue reward on a particular encounter? The answer may be the level of incentive salience (‘wanting’) that is dynamically generated by mesocorticolimbic brain systems, influenced especially by dopamine and opioid neurotransmission in the nucleus accumbens ( NA c) at that moment. We tested the ability of dopamine stimulation (by amphetamine microinjection) vs. mu opioid stimulation [by d‐Ala, nMe‐Phe, Glyol‐enkephalin ( DAMGO ) microinjection] of either the core or shell of the NA c to amplify cue‐triggered levels of motivation to pursue sucrose reward, measured with a Pavlovian‐Instrumental Transfer ( PIT ) procedure, a relatively pure assay of incentive salience. Cue‐triggered ‘wanting’ in PIT was enhanced by amphetamine or DAMGO microinjections equally, and also equally at nearly all sites throughout the entire core and medial shell (except for a small far‐rostral strip of shell). NA c dopamine/opioid stimulations specifically enhanced CS + ability to trigger phasic peaks of ‘wanting’ to obtain UCS , without altering baseline efforts when CS + was absent. We conclude that dopamine/opioid stimulation throughout nearly the entire NA c can causally amplify the reactivity of mesocorticolimbic circuits, and so magnify incentive salience or phasic UCS ‘wanting’ peaks triggered by a CS +. Mesolimbic amplification of incentive salience may explain why a particular cue encounter can become irresistibly tempting, even when previous encounters were successfully resisted before. Surges in the level of motivation elicited by reward cues (i.e., changes cue‐triggered ‘wanting’) are mediated by opioid and‐or dopamine stimulations that increase reactivity of mesocorticolimbic brain circuits involving the nucleus accumbens, which dynamically compute incentive salience for a cue. Nearly the entire medial shell and the entire core can similarly mediate dopamine and opioid enhancements.