THE LONG-TERM IMPACT OF PREVIOUS COCAINE SELF-ADMINISTRATION ON DECISION-MAKING AND STRIATAL CIRCUITRY
Burton, Amanda Claire
Roesch, Matthew R
MetadataShow full item record
Current theories of addiction suggest that impaired decision-making observed in individuals that chronically abuse drugs reflects a decrease in goal-directed behaviors and an increase in habitual behaviors governed by neural representations of response-outcome and stimulus-response associations, respectively. The striatum is a critical input component to the basal ganglia, which is a complex set of subcortical brain structures involved in the selection and execution of actions. Striatal sub-regions are some of the first brain regions to be affected by drugs of abuse, yet we still do not fully understand how decision-making and neural correlates in these regions are affected by drug exposure or disruptions within the circuit. My project was designed to study behavioral and neural changes in the striatum after previous cocaine self-administration or pharmacological lesion while rats perform a complex decision-making task. I therefore implemented a cocaine self-administration or pharmacological lesion protocol and recorded from single neurons in striatal sub-regions, specifically the nucleus accumbens core (NAc) and dorsal lateral striatum (DLS), during performance of an odor-guided decision-making task in which reward contingencies often changed. This task independently manipulated value of expected reward by changing the delay to or size of reward across a series of blocks of trials. I found that previous cocaine self-administration made rats more impulsive, biasing choice behavior toward more immediate reward. After cocaine exposure, there were fewer task-responsive neurons in the NAc and in those that remained we observed diminished directional and value encoding compared to controls. Surprisingly, in the DLS I found evidence of increased response-outcome associations and no evidence of enhanced stimulus-response associations after cocaine exposure. After disrupting communication between the NAc and DLS, I found evidence of enhanced stimulus-response associations in the DLS during task performance. This suggests that cocaine exposure impacts decision-making and neural activity in the striatum that manifests in more complex ways than simply disrupting striatal circuitry as current theories of addiction suggest.