Dissecting the contribution of mu and kappa opioid receptor signalling in effort and delay-related cost/benefit decision making.

RATIONALE: While novel compounds targeting mu and kappa opioid receptors show promise for treating psychiatric cognitive and motivational deficits, their underlying mechanisms remain unclear. Specifically, we lack a precise understanding of how these receptors regulate reward-related cost-benefit decision-making. OBJECTIVES: To determine the contribution of mu and kappa opioid receptor signalling in modulating effort and delay related decisions in male and female rats. METHODS: Separate cohorts of rats were well-trained on effort or delay discounting tasks or different reward magnitude discriminations. Effort and delay tasks had rats choose between no-cost, small (2 or 1 pellet) rewards and high-cost larger, 4-pellet reward associated with effort requirements (1-20 lever presses) or delays (0-45 s), that increased across blocks of trials. Magnitude discriminations entailed choice between large and small (or no) rewards of equal cost. Rats then received vehicle or 1-10 mg of antagonists targeting mu (naloxone) or kappa (aticaprant) opioid receptors. RESULTS: Naloxone reduced effort-related choice and response vigor and increased choice latency and omissions in both sexes, though females were more sensitive to lower doses. Aticaprant did not affect effort discounting or other motivational measures on this task. Neither drug affected choice on delay discounting, although both drugs increase choice latencies, and aticaprant increased omissions in females on this task. Naloxone had comparatively muted effects on choice during reward magnitude discriminations, that varied across sex and task. CONCLUSIONS: These results point to a selective contribution of mu opioid receptor signalling in modulating reward-related decisions involving effort, but not delay costs.