Enhanced Risky Choice in Male Rats Elicited by the Acute Pharmacological Stressor Yohimbine Involves Prefrontal Dopamine D1 Receptor Activation

Abstract

Background Acute stress alters risk-based decision making, however, the underlying neural and neurochemical substrates are underexplored. Given their well-documented stress-inducing effects in humans and laboratory animals, glucocorticoids such as cortisol and corticosterone and the α2-adrenoceptor antagonist yohimbine represent potent pharmacological tools to mimic some characteristics of acute stress. Methods Here, we analyzed the effects of the pharmacological stressors corticosterone and yohimbine given systemically on risk-based decision making in male rats. Moreover, we investigated whether pharmacological stressor effects on risk-based decision making involve dopamine D1 receptor stimulation in the dorsal prelimbic cortex (PL). We used a risk discounting task that requires choosing between a certain/small reward lever that always delivered one pellet and a risky/large reward lever which delivered four pellets with a decreasing probability across subsequent trials. Results Systemic administration of yohimbine increased the preference for the risky/large reward lever. By contrast, systemic single administration of corticosterone did not significantly promote risky choice. Moreover, co-administration of corticosterone did not enhance the effects of yohimbine on risky choice. The data further show that the increased preference for the risky/large reward lever under systemic yohimbine was lowered by a concurrent pharmacological blockade of dopamine D1 receptors in the PL. Conclusions Our rodent data provide causal evidence that stimulation of PL D1 receptors may represent a neurochemical mechanism by which the acute pharmacological stressor yohimbine, and possibly non-pharmacological stressors as well, promote risky choice.