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 (NAc) 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 NAc 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). NAc 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 NAc 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.

Nucleus Accumbens Acetylcholine Receptors Modulate Dopamine and Motivation

“…Activating mAChR autoreceptors on striatal cholinergic interneurons, which can decrease acetylcholine tone at nAChRs on dopamine terminals, can also augment terminal dopamine release to high-frequency stimulation (Shin et al, 2015;Threlfell et al, 2010). Not only is it well established that reward-predictive cues trigger burst firing in dopamine cells (Schultz, 2001), but there is growing evidence that the resulting dopamine release in the NAc mediates cue-motivated instrumental behavior (Lex and Hauber, 2008;Ostlund et al, 2014b;Peciña and Berridge, 2013). Combined, these data suggest that blockade of nAChR could enhance the dopamine response to reward-predictive cues, whereas antagonizing mAChRs could blunt it.…”

“…The behavioral effects of NAc nAChR and mAChR inactivation were complimented by data showing a corresponding influence of these treatments to enhance or attenuate, respectively, cue onset-evoked NAc dopamine signaling, which has been both correlated with (Aitken et al, 2016;Ostlund et al, 2014b;Wassum et al, 2013) and causally implicated in (Lex and Hauber, 2008;Peciña and Berridge, 2013;Wyvell and Berridge, 2000) the motivating influence of cues over reward-seeking activity. Of note, under control conditions, dopamine was found to be elevated at CS + onset and to return to baseline within~30 s, similar to our recent report (Aitken et al, 2016), but shorter-lasting than the cueevoked dopamine response detected during PIT in the earlier work (Wassum et al, 2013).…”

Opioid Hedonic Hotspot in Nucleus Accumbens Shell: Mu, Delta, and Kappa Maps for Enhancement of Sweetness “Liking” and “Wanting”

“…An anatomically localized "hedonic hotspot" has been found within the rostrodorsal quadrant of NAc medial shell: an approximately cubic-millimeter sized subregion where mu opioid stimulation via microinjection of DAMGO can double the hedonic impact of sweet tastes (Peciña and Berridge, 2005;Smith andBerridge, 2005, 2007;Smith et al, 2011). By contrast, the same -opioid stimulation in other subregions of medial shell fails to enhance "liking" reactions to sucrose (Peciña and Berridge, 2005).…”

“…By contrast, the same -opioid stimulation in other subregions of medial shell fails to enhance "liking" reactions to sucrose (Peciña and Berridge, 2005). As part of a larger functional circuit, the NAc hotspot interacts with a second anatomical hotspot in the ventral pallidum to amplify "liking" reactions to sweetness (Smith and Berridge, 2007;Smith et al, 2011).…”

Orexin in Rostral Hotspot of Nucleus Accumbens Enhances Sucrose ‘Liking’ and Intake but Scopolamine in Caudal Shell Shifts ‘Liking’ Toward ‘Disgust’ and ‘Fear’

“…Conversely, in caudal shell, agonist microinjections reveal a 'hedonic coldspot', where opioid stimulation suppresses sucrose hedonic impact (Castro and Berridge, 2014;Pecina and Berridge, 2005). By contrast to the localized hotspot for sweetness 'liking', mu-opioid stimulations increase motivation to eat much more widely and homogeneously throughout the entire NAc shell (and in related structures), measured as increases in cue-triggered 'wanting' to obtain food rewards (eg, in instrumental breakpoint and pavlovian-instrumental transfer tests), as well as in food consumption (Castro and Berridge, 2014;Covelo et al, 2014;Maldonado-Irizarry et al, 1995;Pecina and Berridge, 2005;Pecina and Berridge, 2013;Smith and Berridge, 2005;Smith et al, 2011;Zhang and Kelley, 2000).…”