Amygdala mu-opioid receptors mediate the motivating influence of cue-triggered reward expectations

Abstract

Environmental reward-predictive stimuli can retrieve from memory a specific reward expectation that allows them to motivate action and guide choice. This process requires the basolateral amygdala (BLA), but little is known about the signaling systems necessary within this structure. Here we examined the role of the neuromodulatory opioid receptor system in the BLA in such cue-directed action using the outcome-specific Pavlovian-to-instrumental transfer (PIT) test in rats. Inactivation of BLA mu-, but not delta-opioid receptors was found to dose-dependently attenuate the ability of a reward-predictive cue to selectively invigorate the performance of actions directed at the same unique predicted reward (i.e. to express outcome-specific PIT). BLA mu-opioid receptor inactivation did not affect the ability of a reward itself to similarly motivate action (outcome-specific reinstatement), suggesting a more selective role for the BLA mu-opioid receptor in the motivating influence of currently unobservable rewarding events. These data reveal a new role for BLA mu-opioid receptor activation in the cued recall of precise reward memories and the use of this information to motivate specific action plans.

Keywords: Pavlovian-to-instrumental transfer; basolateral amygdala; memory; motivation; rat.

Figure 1. Histological verification of BLA cannula placements

Schematic representation of microinfusion injector tips for Experiment 1 (A; black, delta group; gray, mu group) or Experiment 2 (B). Line drawings of each section taken from (Paxinos & Watson, 1998) −2.8 – 3.3 mm posterior from bregma.

Figure 2. Effect of BLA delta- or mu-opioid receptor inactivation on Pavlovian-to-instrumental transfer

A, B. Trial-averaged lever presses per 2-min period averaged across both levers during the baseline periods compared to pressing during the CS separated for presses on the lever that, in training, delivered the same outcome as predicted by the CS (CS-Same) and pressing on the other available lever (CS-Diff) for the delta- (A) or mu-opioid receptor antagonist (B) group. C, D. Trial-averaged entries into the food-delivery port during the baseline and CS periods for the delta- (C) or mu-opioid receptor antagonist (D) group. Error bars ±s.e.m. *P<0.05, **P<0.01, ***P<0.001.

Figure 3. Effect of BLA mu-opioid receptor inactivation on cue-induced change in lever pressing during Pavlovian-to-instrumental transfer

CS-induced change (CS – Baseline) in lever pressing on action Same v. Different. Dashed line indicates no change from baseline. Error bars ±s.e.m. *P<0.05.

Figure 4. Effect of BLA mu-opioid receptor inactivation on outcome-specific reinstatement

A. Trial-averaged lever presses per 2-min period averaged across both levers during the baseline periods compared to pressing during the 2-min periods following reward delivery, separated for presses on the lever that, in training, delivered the same outcome as the presented reward (Reinstated) and pressing on the other available lever (Non-reinstated). B. Trial-averaged entries into the food-delivery port during the baseline and reward periods. Error bars ±s.e.m. ***P<0.001.