Contributions of the interaction between mu-opioid receptors and dopamine receptors in the regulation of risky decision making.

During decision making, the ability to appropriately weigh potential risks against their associated rewards is necessary to navigate daily life. Prior work has established a critical role for dopamine (DA) D2 receptors (D2Rs) in this process, with activation of these receptors decreasing choice of risky options. Much less is known, however, about how other neuromodulatory systems, such as the endogenous opioid system, contribute to risk-based decision making and whether these systems interact with D2R regulation of risky choice. To begin to address this gap in knowledge, the goals of the current study were to identify the role of mu-opioid receptors (MORs) in decision making involving risk of punishment and to determine whether interactions between MORs and D2Rs are necessary to drive adaptive decision-making behavior. Drug-naïve male and female rats were trained on a punishment-based decision-making task in which rats chose between a small, safe food reward and a larger food reward accompanied by a variable risk of footshock punishment. Following training, effects of a MOR antagonist (Experiment 1), a D2R antagonist and MOR agonist (Experiment 2), a D2R agonist and MOR antagonist (Experiment 3), or an indirect catecholaminergic agonist and MOR antagonist (Experiment 4) on decision making were evaluated. The MOR antagonist naltrexone had no effect on lever presses for the large, risky reward (i.e., risk taking) or for the small, safe reward in either sex. The MOR agonist morphine, regardless of D2R inactivation, also did not affect risk taking, although it did decrease lever presses for the small, safe reward. When MORs were blocked with an antagonist, a selective D2R agonist caused a significant decrease in risk taking relative to vehicle conditions. The indirect catecholamine agonist amphetamine, however, decreased risk taking irrespective of whether MORs were blocked. Collectively, these findings suggest that although MOR activation alone is not necessary for decision making involving risk of punishment, the interaction between D2Rs and MORs may be an important mechanism underlying processes contributing to punishment-based decision making. Future studies will expand on this work by identifying where in the brain this interaction occurs to influence risk taking.