Addiction is sometimes described as a disorder of decision-making. To make appropriate decisions, people and animals must weigh both the benefits and the costs of the available options. Addicts, however, have difficulty assessing the costs associated with drug use, and will expend a disproportionate degree of physical and mental effort to obtain drug. To understand how this happens, we must first investigate how effort is represented in the brain, and how this representation contributes to the decision to seek rewards. The nucleus accumbens (NAc) - and especially dopamine (DA) signaling in the NAc core - has long been implicated in the exertion of effort to obtain reward. However, it remains unknown how neural signals in the NAc might support the decision to exert effort. Although many individual NAc neurons respond to reward- predictive cues, it is unclear how these neurons encode the effort associated with cues and choices, especially in the moment when the animal decides whether to pursue an effortful option. Moreover, it is not known how DA input to the NAc contributes to effort-related signaling. To address these issues, rats will be trained to perform a task in which they decide between two options (levers) that are associated with different levels of effort (number of required lever presses) and/or different amounts of sucrose reward. While rats are making these decisions, we will record the firing activity of individual neurons in the NAc. We hypothesize that NAc neurons will encode both reward and effort levels in such a way that their activity may contribute to the weighing of options and/or the implementation of the resulting decision. Next, we will microinject DA receptor blockers into NAc core and observe the effect on rats'choices. We expect that these drugs will disrupt effort-based decision-making such that rats will become unwilling to exert more effort to obtain more reward. Finally, using an innovative technique, we will microinject DA receptor blockers into the NAc while simultaneously recording the neural activity of NAc neurons. We hypothesize that blocking DA receptors will disrupt the representation of effort information by NAc neurons. Taken together, these experiments will clarify the role of the NAc and its dopaminergic inputs in the circuits that underlie decision-making processes in the normal brain. This is a key step towards understanding how these circuits might go awry in the addicted brain, potentially opening a path towards developing or improving therapies for drug addiction.
Drug addicts make dysfunctional decisions when they are seeking drugs, and are willing to expend an extraordinary amount of effort to obtain drugs. The proposed experiments will shed light on how decisions about whether or not to exert effort take place in the brain. This research could lead to new avenues for therapies to help people recover from drug addiction.
| Morrison, Sara E; Bamkole, Michael A; Nicola, Saleem M (2015) Sign Tracking, but Not Goal Tracking, is Resistant to Outcome Devaluation. Front Neurosci 9:468 |
| Morrison, Sara E; Nicola, Saleem M (2014) Neurons in the nucleus accumbens promote selection bias for nearer objects. J Neurosci 34:14147-62 |
