Disruptions in effort-based decision-making following acute optogenetic stimulation of ventral tegmental area...

The dopamine system has been implicated in decision-making particularly when associated with effortful behavior. We examined acute optogenetic stimulation of dopamine cells in the ventral tegmental area (VTA) as mice engaged in an effort-based decision-making task. Tyrosine hydroxylase-Cre mice were injected with Cre-dependent ChR2 or eYFP control virus in the VTA. While eYFP control mice showed effortful discounting, stimulation of dopamine cells in ChR2 mice disrupted effort-based decision-making by reducing choice toward the lever associated with a preferred outcome and greater effort. Surprisingly, disruptions in effortful discounting were observed in subsequent test sessions conducted in the absence of optogenetic stimulation, however during these sessions ChR2 mice displayed enhanced high choice responding across trial blocks. These findings suggest increases in VTA dopamine cell activity can disrupt effort-based decision-making in distinct ways dependent on the timing of optogenetic stimulation.