Distinct Opioid Circuits Determine the Palatability and the Desirability of Rewarding Events

Distinct opioid circuits determine the palatability and the desirability of rewarding events K. M. Wassuma,b,1, S. B. Ostlunda,b,c, N. T. Maidmenta,b, and B. W. Balleinea,b,c,d,1 aDepartment of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, CA 90024; bBrain Research Institute, University of California, Los Angeles, CA 90095; cDepartment of Psychology, University of California, Los Angeles, CA 90095; and dBrain and Mind Research Institute, University of Sydney, NSW 2050, Australia Communicated by Charles R. Gallistel, Rutgers, The State University of New Jersey, Piscataway, NJ, June 4, 2009 (received for review January 29, 2009) It generally is assumed that a common neural substrate mediates both We sought to evaluate these alternatives by comparing the role the palatability and the reward value of nutritive events. However, of opioid receptor-related processes in the nucleus accumbens shell, recent evidence suggests this assumption may not be true. Whereas the ventral pallidum, and the basolateral amygdala using an animal opioid circuitry in both the nucleus accumbens and ventral pallidum model that permitted concurrent assessment of changes in liking, or has been reported to mediate taste-reactivity responses to palatable palatability, and the incentive value of a reward. In both humans events, the assignment of reward or inventive value to goal-directed and rats increased food deprivation increases the palatability of actions has been found to involve the basolateral amygdala. Here we food, as assessed by verbal hedonic evaluation or the incidence of found that, in rats, the neural processes mediating palatability and positive facial responses and certain lick patterns, in addition to increasing the performance of food-related actions (21, 22). How- incentive value are indeed dissociable. Naloxone infused into either ever, this last effect is not an immediate consequence of the the ventral pallidum or nucleus accumbens shell blocked the increase motivational shift; rather, it depends on learning about the food’s in sucrose palatability induced by an increase in food deprivation increased value through consummatory contact in the new state. without affecting the performance of sucrose-related actions. Con- Thus, in rats, an increase in food deprivation increases the perfor- versely, naloxone infused into the basolateral amygdala blocked food mance of lever-pressing actions that gain access to a palatable food deprivation-induced changes in sucrose-related actions without reward only after the rats have been given the opportunity to affecting sucrose palatability. This double dissociation of opioid- consume that food in the deprived state (23, 24). This phenomenon, mediated changes in palatability and incentive value suggests that called ‘‘incentive learning’’, is considered to model the incentive the role of endogenous opioids in reward processing does not depend value of rewards or the state of desire evoked to explain the pursuit on a single neural circuit. Rather, changes in palatability and in the of goals (23, 24). Here we used this incentive learning paradigm to incentive value assigned to rewarding events seem to be mediated by compare changes in incentive value with changes in the palatability distinct neural processes. responses that reflect reward liking in rats to assess whether these components of reward processing are mediated by a common incentive value ͉ taste reactivity ͉ instrumental conditioning ͉ neural substrate. opioid receptors ͉ basolateral amygdala Rats were maintained in a relatively sated state and trained, as illustrated in Table 1, to seek a sucrose reward using a procedure in which they had to press a lever (‘‘seeking lever’’) to get access to oal-directed actions are the means by which we exert control a second lever (‘‘taking lever’’) that delivered the sucrose (15, 25). Gover our environment in the service of our desires. The This task has been found to establish a reward-seeking action decision to engage in such actions is based largely on the degree specifically sensitive to incentive learning (15, 25). Next, we gave the to which the goal, or reward, is valued or ‘‘desired’’ (1). Theories rats the opportunity for incentive learning by allowing them to regarding the neural bases of reward processing generally as- consume the sucrose after an increase in food deprivation. To sume that the pleasure elicited during contact with rewarding evaluate the role of opioid processes in establishing the current events and the desirability, or incentive value, of those events are desirability of the sucrose, we gave microinfusions of either the mediated by a common process (2–4). However, recent exper- opioid antagonist naloxone or vehicle into the nucleus accumbens iments assessing the neural bases of reward have found evidence shell, ventral pallidum, or basolateral amygdala before consumma- of multiple candidate regions associated with what seem to be tory contact (Fig. S1). During this session we evaluated the palat- distinct aspects of reward processing. Using consumption and ability responses elicited during consumption of the sucrose using taste-reactivity measures of palatability in rodents, several a contact lickometer, a measure previously reported to provide an assessment of reward liking similar to that used by Berridge and groups have reported evidence of an opioid receptor-mediated colleagues (26, 27) (See also SI Results and Fig. S2). We next network within the circuitry of the nucleus accumbens shell and examined the effects of the naloxone infusions on incentive learning ventral pallidum mediating hedonic processing or reward ‘‘lik- by assessing, off drug, the subsequent performance of goal-directed ing’’ based on the palatability-enhancing effects of locally in- reward-seeking responses in an unrewarded test (i.e., in the absence fused opioid agonists (5–8). However, although opioid processes of any further experience with the reward). often have been proposed to convey the affective properties of natural rewards (9, 10), opioid peptide-containing neurons and Results receptors are present in multiple basal forebrain regions (11, 12) Infusing Naloxone into Either the Nucleus Accumbens Shell or Ventral implicated not in reward hedonia but rather in the learning Pallidum Blocks Changes in Palatability Without Affecting Incentive process that mediates goal-directed actions. In particular, several studies have found the opioid receptor-rich basolateral amygdala (13) to be important for encoding the incentive value of the Author contributions: K.M.W., S.B.O., N.T.M., and B.W.B. designed research; K.M.W. and S.B.O. performed research; K.M.W. analyzed data; and K.M.W., N.T.M., and B.W.B. wrote rewards that support the performance of goal-directed actions in the paper. rats (14–17). Although it is possible that opioid-related processes The authors declare no conflict of interest. form an integrated reward network (18), the neural processes 1To whom correspondence may be addressed. E-mail: [email protected] or balleine@ mediating palatability, or liking, may be distinct from those that med.usyd.edu.au. establish the desirability of the consequences of goal-directed This article contains supporting information online at www.pnas.org/cgi/content/full/ actions (19, 20). 0905874106/DCSupplemental. 12512–12517 ͉ PNAS ͉ July 28, 2009 ͉ vol. 106 ͉ no. 30 www.pnas.org͞cgi͞doi͞10.1073͞pnas.0905874106 Downloaded by guest on October 1, 2021 Table 1. Design of incentive learning experiments Nucleus Accumbens Shell Non-Contingent A Palatability 2h 7.5 23h Revaluation Test * * Training Test Day 1 Test Day 2 7.0 6.5 2 h deprivation Naloxone or Vehicle 2 h or 23 h deprivation 6.0 5.5 LPS 3 [LPD 3 Suc] 2 h deprivation: Suc LPS 3 [LPD 3 ø] 5.0 Naloxone or Vehicle 4.5 23 h deprivation: Suc Licks/Second 4.0 3.5 Rats deprived of food for 2 h were trained to press a seeking lever (LPS)to Vehicle Naloxone gain access to a second lever that delivered a sucrose solution (Suc) B Reward Seeking Actions (LPD3SUC). They then were maintained in the 2 h food-deprived condition or 250 * ** were shifted to 23 h food deprivation and were allowed to consume the 200 sucrose after an infusion of naloxone or vehicle into the nucleus accumbens shell, ventral pallidum, or basolateral amygdala. The effect of the infusions on 150 palatability responses was assessed in this re-evaluation session. The effect of 100 re-exposure and the influence of naloxone on that effect in rats deprived of food for 2 h or 23 h were assessed in a test conducted on the levers in extinction 50 (i.e., in the absence of further experience with the sucrose). (See SI Methods Seeking % Baseline Seeking % 0 for full details.) Vehicle Naloxone Drug at Re-exposure Learning. As illustrated in Table 1, this experiment was conducted Fig. 1. Naloxone infused into the nucleus accumbens shell blocks food in 3 phases involving initial training, incentive learning, and test. All deprivation-induced increases in palatability without affecting incentive the rats acquired and maintained lever-pressing performance, and, learning. (A) Palatability. Rats, deprived of food for either 2 h (control) or 23 h, in the final session of training, performed the seeking lever response received an infusion of vehicle or naloxone into the nucleus accumbens shell immediately before re-exposure to sucrose; during the exposure, licking at a rate of 9.7 presses (earning 2.3 rewards) per min in the nucleus frequency data were measured. Assessment by 2-way ANOVA of lick fre- accumbens shell-cannulated group and 6.3 presses (1.5 rewards) per quency found no main effect of drug (F1,24 ϭ 2.11, P ϭ 0.16) or deprivation min in the ventral pallidum-cannulated group. (F1,24 ϭ 1.91, P ϭ 0.18) but did find a significant interaction between drug and The effect of intra-nucleus accumbens shell and intra-ventral deprivation (F1,24 ϭ 7.88, P ϭ 0.009).

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