Drugs, Decisions, Desire, and DREADDs: Exploring Ventral Pallidum GABAergic Neuron Function in Motivated Behavior

A fundamental function of the brain is to navigate a dynamic world and generate appropriate behaviors in pursuit of rewards (e.g., food, water) and avoidance of harm (e.g., predators). These fundamental functions go awry in psychiatric disorders like addiction, yet the particular neural circuits involved in balancing reward seeking and harm avoidance remain largely unresolved. Ventral pallidum (VP) has emerged as a convergence point of motivational information, and, as such, regulates motivation for diverse natural rewards as well as drugs of abuse. While most work in VP has assessed its function in appetitive motivation, emerging work has revealed that VP is critical for aversive motivation/learning. In part, VP supports both appetitive and aversive motivation via functionally distinct neurotransmitter-defined neuron populations. Specifically, VP GABAergic (VPGABA) neurons are thought to be critical for appetitive processes, whereas VP glutamatergic neurons are important for aversive processes. However, most goals and actions are rife with potential consequences, and thus adaptive behavior must appropriately weigh these potential consequences when seeking rewards. Here, I explore the function of VPGABA neurons under motivational conflict, as well as appetitive and aversive motivation. To do so, I employ a suite of decision making and relapse behavioral models in rats accompanied by cell-type specific chemogenetics and immunohistochemical approaches to dissect the behavioral function of VPGABA neurons. We found that 1) chemogenetic inhibition of VPGABA neurons attenuates cocaine and remifentanil seeking across rat relapse models, 2) stimulating VPGABA neurons augments remifentanil seeking in a ‘dangerous’ context in which rats had previously received footshock, and 3) inhibiting VPGABA neurons diminishes an animals’ willingness to exert risky behavior or exert effort to obtain valuable food rewards. These findings generally support the notion that VPGABA neurons may control the deployment of cognitive resources to overcome obstacles, pursue goals in the face of adversity, and weigh whether a goal is worth pursuing. Further illuminating the neural circuits of motivation will potentially yield novel neuroscience-based interventions for treating psychiatric disorders like addiction in the future