Dopaminergic and Glutamatergic Regulation of Effort- and Delay-Based Decision Making

Abstract

Cost/benefit decisions regarding the relative effort or delay costs associated with a particular response are mediated by distributed dopaminergic and glutamatergic neural circuits. The present study assessed the contribution of dopamine and NMDA glutamate receptors in these different forms of decision making using novel effort-and delay-discounting procedures. In the effort-discounting task, rats could either emit a single response on a low-reward lever to receive two pellets, or make 2, 5, 10, or 20 responses on a high-reward (HR) lever to obtain four pellets. In the delay-discounting task, one press of the HR lever delivered four pellets after a delay (0.5-8 s). A third task (effort-discounting with equivalent delays) was similar to the effort-discounting procedure, except that the relative delay to reward delivery was equalized across response options. The dopamine receptor antagonist flupenthixol reduced choice of the HR lever under all three testing conditions, indicating that dopamine antagonism alters effort-based decision making independent of any contribution of delay. Amphetamine exerted dose-dependent, biphasic effects; a higher dose (0.5 mg/kg) increased effort discounting, whereas a lower dose (0.25 mg/kg) reduced delay discounting. The noncompetitive NMDA antagonist ketamine (5 mg/kg) increased effort and delay discounting, but did not affect choice on the effort with equivalent delays task, indicating a reduced tolerance for delayed rewards. These findings highlight the utility of these procedures in pharmacologically dissociating the neurochemical mechanisms underlying these different, yet interrelated forms of decision making. Furthermore, they suggest that dopamine and NMDA receptors make dissociable contributions to these different types of cost-benefit analyses.

Functional Genetic Variation in Dopamine Signaling Moderates Prefrontal Cortical Activity During Risky Decision Making

“…In line with this view, animal studies measuring dopamine efflux using microdialysis have shown contributions of the PFC and striatum in integrating reward, delay and uncertainty signals (St Onge et al, 2012), and pharmacological disruption of dopamine signaling produces effects on reward-driven behavior (Floresco et al, 2008). A role of striatal D2-type receptors in prefrontal cortical function has been inferred from rates of glucose metabolism (Volkow et al, 2001), and it has been proposed that abnormal activity of dopaminergic neurons may enhance stimulusreward associations (Wise, 2002) and the inhibition of reward-seeking behavior depends upon activity in corticostriatal projections (Jentsch and Taylor, 1999).…”

Disparate cocaine-induced locomotion as a predictor of choice behavior in rats trained in a delay-discounting task

“…The results from the present study do offer some insight into the consequences of the neurobiological differences between LCRs and HCRs. Because the DAT is a primary pharmacological target of AMPH, and alterations in DA signaling are important for behavior in the delay-discounting task (Floresco et al, 2007;van Gaalen et al, 2006), the differential effects we observed for AMPH in LCRs compared to HCRs are a likely reflection of known differences in DAT function between these phenotypes (Sabeti et al, 2003;Briegleb et al, 2004). Importantly, impulsive choice behavior may be influenced by an interaction between DAergic and 5-HTergic function (Winstanley et al, 2005(Winstanley et al, , 2006b, and this could be relevant for differences in choice behavior between LCRs and HCRs.…”

The Roles of Dopamine and Serotonin in Decision Making: Evidence from Pharmacological Experiments in Humans

“…The specificity of the dopamine contribution to decision making is underpinned by the demonstration of a double dissociation of changes in effort vs delay discounting following the administration of the mixed D 2 receptor antagonist, haloperidol and para-chlorophenylalanine (pCPA), indicating greater involvement of the D 2 family of receptors in the former and of serotonin activity in the latter forms of behavioral choice (Denk et al, 2005). In addition, the influence of dopamine upon these forms of decision-making function is likely to involve complex interactions with other neurotransmitter systems, such as glutamate, that also play a pivotal role in motivation and reinforcement (Floresco et al, 2008).…”