A characterization of behavior and monoamine interactions during conditioned avoidance maintained in a within‐session behavioral economic avoidance task

Abstract

The mesolimbic dopamine (DA) system is generally considered to be a reward pathway, however, It is becoming increasingly evident that dopamine release events also process aversion and influence aversively motivated behavior. To investigate the role that dopamine plays in the motivation to avoid, we first developed an economics‐based shock avoidance task in which rats are given the opportunity to avoid electrical foot‐shock. Within each session, we provide rats with the opportunity to avoid footshock across a range of prices (response requirement/mA shock). A stimulus light, or warning signal, placed above the lever signals the opportunity to avoid impending footshock. Using fast‐scan cyclic voltammetry, we determined that dopamine concentration at both the warning signal and successful avoidance decreases with price. However, an attenuation of avoidance and dopamine release at session onset developed over the course of training. It is possible that session onset begins to predict an aversive session terminus because sessions terminate after a minimum of 15 footshocks occur. To further characterize this initial suppression we are currently measuring ultrasonic vocalizations (USVs) during the acquisition of avoidance in the behavioral economics task. We predict that 22khz USVs will develop at session onset in a manner that conincides with both the attenuation of dopamine release and avoidance. While characterizing a novel approach to measure conditioned fear is worthwhile in its own right, we primarily developed our task to measure changes in the price rats will pay to avoid. We measure the price rats will pay to avoid by using demand curves. Demand curves are a common tool used by economists to measure price sensitivity that depict the relationship between consumption (mA footshock avoided) and price (responses/mA). The rate at which demand curves decay can be used to make inferences regarding the value individuals place on the commodity being consumed. If the slope decays at a faster rate we would infer that the value to avoid is decreased because the rats are paying less to avoid. Using optogenetics, we found that increasing dopamine release at successful avoidance increases the price rats will pay for cocaine. Follow‐up optogenetic studies are investigating the role of the habenula‐RMTg‐mesolimbic dopamine circuitry. We predict that exciting glutamate neurons in the habenula will produce opposite behavioral effects to those occurring from direct dopamine stimulation. We are also beginning to compare the effects of discrete monoamine systems. To begin, we are simply pre‐treating rats with dopamine, serotonin and norepinephrine uptake inhibitors. Based on our preliminary optogenetics data, we predict that the dopamine uptake inhibitor will increase the price rats will pay to avoid whereas, serotonin and norephinephreine manipulations will produce distinct effects.Support or Funding InformationThis work was supported by the National Science Foundation Grant IOS‐1557755, the National Institutes of Health Grant R03DA038734, the Boettcher Young Investigator Award and the National Alliance for Research on Schizophrenia and Depression Young Investigator Award (E.B.O.)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.