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

Development of behavioral preferences for the optimal choice following unexpected reward omission is mediated by a reduction of D 2‐like receptor tone in the nucleus accumbens

To survive in a dynamic environment, animals must identify changes in resource availability and rapidly apply adaptive strategies to obtain resources that promote survival. We have utilised a behavioral paradigm to assess differences in foraging strategy when resource (reward) availability unexpectedly changes. When reward magnitude was reduced by 50% (receive one reward pellet instead of two), male and female rats developed a preference for the optimal choice by the second session. However, when an expected reward was omitted (receive no reward pellets instead of one), subjects displayed a robust preference for the optimal choice during the very first session. Previous research shows that, when an expected reward is omitted, dopamine neurons phasically decrease their firing rate, which is hypothesised to decrease dopamine release preferentially affecting D 2‐like receptors. As robust changes in behavioral preference were specific to reward omission, we tested this hypothesis and the functional role of D 1‐ and D 2‐like receptors in the nucleus accumbens in mediating the rapid development of a behavioral preference for the rewarded option during reward omission in male rats. Blockade of both receptor types had no effect on this behavior; however, holding D 2‐like, but not D 1‐like, receptor tone via infusion of dopamine receptor agonists prevented the development of the preference for the rewarded option during reward omission. These results demonstrate that avoiding an outcome that has been tagged with aversive motivational properties is facilitated through decreased dopamine transmission and subsequent functional disruption of D 2‐like, but not D 1‐like, receptor tone in the nucleus accumbens. This study investigates the role of dopamine receptors in the nucleus accumbens in altering behavior in response to the omission of an expected reward. Similarly to controls, multiple doses of a D 1‐like receptor agonist, D 1‐like receptor antagonist, and D 2‐like receptor antagonist do not prevent subjects from developing a robust behavioral preference for the rewarded lever and avoiding the omitted‐reward lever during the first session of reward omission. However, the D 2‐like agonist quinpirole dose‐dependently blocks a behavioral preference for the rewarded lever, suggesting that reductions in D 2‐like receptor tone are necessary for altering behavior away from an aversive option and toward the optimal choice.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/99645/1/ejn12253.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/99645/2/ejn12253-sup-0001-Supplement.pd

Dopamine and opioid systems interact within the nucleus accumbens to maintain monogamous pair bonds

Prairie vole breeder pairs form monogamous pair bonds, which are maintained through the expression of selective aggression toward novel conspecifics. Here, we utilize behavioral and anatomical techniques to extend the current understanding of neural mechanisms that mediate pair bond maintenance. For both sexes, we show that pair bonding up-regulates mRNA expression for genes encoding D1-like dopamine (DA) receptors and dynorphin as well as enhances stimulated DA release within the nucleus accumbens (NAc). We next show that D1-like receptor regulation of selective aggression is mediated through downstream activation of kappa-opioid receptors (KORs) and that activation of these receptors mediates social avoidance. Finally, we also identified sex-specific alterations in KOR binding density within the NAc shell of paired males and demonstrate that this alteration contributes to the neuroprotective effect of pair bonding against drug reward. Together, these findings suggest motivational and valence processing systems interact to mediate the maintenance of social bonds

Chemical Gradients within Brain Extracellular Space Measured using Low Flow Push–Pull Perfusion Sampling in Vivo

Although populations of neurons are known to vary on the micrometer scale, little is known about whether basal concentrations of neurotransmitters also vary on this scale. We used low-flow push–pull perfusion to test if such chemical gradients exist between several small brain nuclei. A miniaturized polyimide-encased push–pull probe was developed and used to measure basal neurotransmitter spatial gradients within brain of live animals with 0.004 mm³ resolution. We simultaneously measured dopamine (DA), norepinephrine, serotonin (5-HT), glutamate, γ-aminobutyric acid (GABA), aspartate (Asp), glycine (Gly), acetylcholine (ACh), and several neurotransmitter metabolites. Significant differences in basal concentrations between midbrain regions as little as 200 μm apart were observed. For example, dopamine in the ventral tegmental area (VTA) was 4.8 ± 1.5 nM but in the red nucleus was 0.5 ± 0.2 nM. Regions of high glutamate concentration and variability were found within the VTA of some individuals, suggesting hot spots of glutamatergic activity. Measurements were also made within the nucleus accumbens core and shell. Differences were not observed in dopamine and 5-HT in the core and shell; but their metabolites homovanillic acid (460 ± 60 nM and 130 ± 60 nM respectively) and 5-hydroxyindoleacetic acid (720 ± 200 nM and 220 ± 50 nM respectively) did differ significantly, suggesting differences in dopamine and 5-HT activity in these brain regions. Maintenance of these gradients depends upon a variety of mechanisms. Such gradients likely underlie highly localized effects of drugs and control of behavior that have been found using other techniques