Dopamine Modulation of Choice Behavior Following Unexpected Reward Omission

Being able identify decreases in resource availability and alter motivated behavior accordingly is evolutionarily adaptive. Additionally, the neurobiological mechanisms that facilitate these basic foraging skills in animals are thought to be utilized in other forms of goal directed cognition in humans. To study how the brain mediates such behaviors, we adapt an operant behavioral task in which laboratory rats can earn food rewards from two distinct levers. We find that when one lever is extinguished, while the other lever continues to be reinforced, both male and female rats quickly identify this contingency change and develop a choice preference for the rewarded lever. Previous electrophysiology studies of putative midbrain dopamine (DA) neurons have revealed brief pauses in neuronal activity when an expected reward is omitted, which is thought to briefly decrease DA transmission in terminal regions, such as the nucleus accumbens (NAc). Additionally, decreases in DA transmission have been hypothesized to be signaled preferentially through D2 receptors. Other studies, however, have proposed that extra-cellular DA levels over longer periods of time may play a role in motivation and behavioral flexibility. To test these hypotheses, we employ one-minute sampling microdialysis and fast-scan cyclic voltammetry (FSCV) in the NAc. Microdialysis experiments reveal an increase in DA concentration, lasting multiple minutes, following the omission of an expected rewarded. These increases in DA concentration correlate to observed increases in motivational vigor and exploratory behaviors. In contrast, FSCV reveals brief decreases in DA transmission when the expected reward is omitted, consistent with previous electrophysiology studies. Furthermore, holding D2 receptor tone, through site-specific microinfusion of a D2-like agonist into the NAc, attenuates the behavioral preference for the rewarded option. Together, these experiments reveal dynamic changes in DA transmission over multiple time scales when an expected reward is omitted. Tonic increases in DA concentration may motivate the animal to employ alternate behavioral strategies, while the phasic decreases are likely involved in redirecting choice behavior away from the non-rewarded option. This series of experiments provides novel insight into the complex relationships between DA transmission and motivated behavior during negative changes in reward availability.PhDPsychologyUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/109040/1/stransky_1.pd