Distinct opioid circuits determine the palatability and the desirability of rewarding events

Abstract

It generally is assumed that a common neural substrate mediates both the palatability and the reward value of nutritive events. However, recent evidence suggests this assumption may not be true. Whereas opioid circuitry in both the nucleus accumbens and ventral pallidum has been reported to mediate taste-reactivity responses to palatable events, the assignment of reward or inventive value to goal-directed actions has been found to involve the basolateral amygdala. Here we found that, in rats, the neural processes mediating palatability and incentive value are indeed dissociable. Naloxone infused into either the ventral pallidum or nucleus accumbens shell blocked the increase in sucrose palatability induced by an increase in food deprivation without affecting the performance of sucrose-related actions. Conversely, naloxone infused into the basolateral amygdala blocked food deprivation-induced changes in sucrose-related actions without affecting sucrose palatability. This double dissociation of opioid-mediated changes in palatability and incentive value suggests that the role of endogenous opioids in reward processing does not depend on a single neural circuit. Rather, changes in palatability and in the incentive value assigned to rewarding events seem to be mediated by distinct neural processes.

Fig. 1.

Naloxone infused into the nucleus accumbens shell blocks food deprivation-induced increases in palatability without affecting incentive learning. (A) Palatability. Rats, deprived of food for either 2 h (control) or 23 h, received an infusion of vehicle or naloxone into the nucleus accumbens shell immediately before re-exposure to sucrose; during the exposure, licking frequency data were measured. Assessment by 2-way ANOVA of lick frequency found no main effect of drug (F_1,24 = 2.11, P = 0.16) or deprivation (F_1,24 = 1.91, P = 0.18) but did find a significant interaction between drug and deprivation (F_1,24 = 7.88, P = 0.009). (The y axis is truncated at 3.5 licks/s based on our observation of this frequency as the floor licking rate). (B) Incentive learning. Incentive learning was assessed off drug in a test of lever-press performance conducted unrewarded. Reward-seeking response rates on test were normalized to response rates during baseline training. Assessment by 2-way ANOVA found a main effect of deprivation (F_1,22 = 21.65, P = 0.0001), no effect of drug (F_1,22 = 0.37 P = 0.54), and no interaction between drug and deprivation (F_1,22 = 0.14 P = 0.71). Error bars represent standard error of the mean. n = 16. *, P < 0.05; **, P < 0.01.

Fig. 2.

Naloxone infused into the ventral pallidum blocks food deprivation-induced increases in palatability without affecting incentive learning. (A) Palatability: see the legend for Fig. 1A. Assessment by 2-way ANOVA of lick frequency data found a main effect of drug (F_1,36 = 5.21, P = 0.03) but no effect of deprivation (F_1,36 = 1.68, P = 0.20) or an interaction between drug and deprivation (F_1,36 = 3.01, P = 0.09). (B) Incentive learning: see the legend for Fig.1B. Assessment by 2-way ANOVA of lever press data found a main effect of deprivation (F_1,27 = 25.31, P < 0.001) and drug (F_1,27 = 5.64, P = 0.02) but no interaction between drug and deprivation (F_1,27 = 1.30, P = 0.26). n = 18. *, P < 0.05; ***, P < 0.001.

Fig. 3.

Intra-basolateral amygdala naloxone blocks incentive learning but does not affect changes in palatability or the retrieval of incentive value. (A) Palatability: see the legend for Fig. 1A. Assessment by 2-way ANOVA of lick frequency data following intra-basolateral amygdala infusion found a main effect of deprivation (F_1,127 = 11.88, P = 0.0008), no effect of drug (F_1,127 = 1.29, P = 0.25), and no interaction between drug and deprivation (F_1,127 = 0.02, P = 0.88). (B) Incentive learning: see the legend for Fig. 1B. Assessment by 2-way ANOVA found a main effect of deprivation (F_1,85 = 8.30, P = 0.005) and drug (F_1,85 = 3.72, P = 0.05) and an interaction between drug and deprivation (F_1,85 = 4.79, P = 0.03). (C) Naloxone on test: seeking response rates, normalized to training baseline, are shown for the rats receiving naloxone immediately before the non-rewarded test. Assessment by 3-way ANOVA found a main effect of deprivation (F_1,127 = 11.90, P = 0.001) and of drug during re-exposure (F_1,127 = 5.95, P = 0.016) but no effect of drug on test (F_1,127 = 2.62, P = 0.11). There was an interaction between drug and deprivation during re-exposure (F_1,127 = 9.58, P = 0.002). No other interactions were significant (all Fs < 1). n = 26 in both replications. *, P < 0.05; **, P < 0.01.

Fig. 4.

Temporal control of incentive learning. Intra-basolateral amygdala naloxone reduces lever pressing across time in an on-baseline test of reward seeking. We conducted 2 sequential tests of lever pressing under a single food-deprivation condition; the first was non-rewarded, and the second, immediately thereafter, was under rewarded conditions. Naloxone or vehicle was infused into the basolateral amygdala immediately before the testing sequence. (A) Seeking responses normalized to baseline responding, for both the non-rewarded (Left) and rewarded (Right) tests. Assessment by 2-way repeated measures ANOVA found no effect of test (F_1,17 = 1.34, P = 0.26) but an effect of drug (F_1,17 = 4.35, P = 0.05) and a marginal interaction between test and drug (F_1,17 = 3.61, P = 0.07). (B) The temporal dynamics of the effect of intra-basolateral amygdala naloxone on reward-seeking responses presented in 4-min bins over the course of the rewarded test, expanding the data presented in the shaded portion of A. Assessment by 2-way repeated measures ANOVA found no overall effect of time (F_3,51 = 2.15 P = 0.11) but a significant effect of drug (F_1,17 = 6.53 P = 0.02) and an interaction between time and drug (F_3,51 = 3.73, P = 0.02). n = 18. *, P < 0.05