δ-Opioid receptors in the accumbens shell mediate the influence of both excitatory and inhibitory predictions on choice.
OBJECTIVE
Stimuli that predict rewarding events can control choice between future actions, and this control could be mediated by δ-opioid receptors in the nucleus accumbens shell (NAc-S). Stimuli predicting the absence of important events can also guide choice, although it remains unknown whether they do so via changes in an accumbal δ-opioid receptor-related process.


METHODS
δ-opioid receptor-eGFP mice were trained to perform two instrumental actions that delivered different food outcomes. Choice between the two actions was then tested in the presence of stimuli paired with either the delivery or the non-delivery of each of the two outcomes. Bilateral infusions of the δ-opioid receptor antagonist naltrindole into the NAc-S were used to determine the role of these receptors at the time of choice and δ-opioid receptor expression in the NAc-S used to assess functional activity.


RESULTS
A stimulus predicting a specific outcome biased choice performance towards the action previously earning that same outcome. In contrast, a stimulus signalling the absence of that outcome biased performance away from the action that delivered that outcome towards actions associated with the absence of that outcome. Both effects were associated with increased δ-opioid receptor expression on the membrane of cholinergic interneurons within the NAc-S. Furthermore, both effects were blocked by naltrindole infused into the NAc-S.


CONCLUSIONS
These findings suggest that δ-opioid receptors in the NAc-S were involved in the effects of predictive learning on choice between actions, whether those predictions involve the presence or absence of specific rewarding events.


BACKGROUND
This article is part of a themed section on Opioids: New Pathways to Functional Selectivity. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-2.
Behavioural Neuroscience Laboratory, Brain and Mind Research Institute, The University of Sydney, Camperdown, NSW, 2006, Australia.
Vincent
V
Laurent
Felix L
FL
Wong
Bernard W
BW
Balleine
D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D002755:Choice Behavior / Q000502:physiology*; D049452:Green Fluorescent Proteins / Q000235:genetics; D008297:Male; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009714:Nucleus Accumbens / Q000502:physiology*; D020318:Rats, Long-Evans; D017465:Receptors, Opioid, delta / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*
D009292:Narcotic Antagonists; D017465:Receptors, Opioid, delta; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D009271:Naltrexone; C055382:naltrindole
Pavlovian-instrumental transfer; backward conditioning; choice; cholinergic interneurons; excitatory conditioning; goal-directed action; inhibitory conditioning; naltrindole; nucleus accumbens shell; δ-opioid receptors