Assessment Of Cell-Type-Specific Excitatory Synaptic Strength In The Dorsolateral Striatum Of Goal-Directed And Habitual Cocaine-Seeking Behavior

With repeated exposure to addictive drugs, there is a shift from drug abuse to drug addiction that is mediated by the transition from goal-directed to habitual control. It is well known that the development of habitual control over behavior relies upon cell-type-specific synaptic changes in both D1 and D2 medium spiny neurons (MSNs) in dorsal striatum. Specifically, habitual behavior is mediated by increased synaptic strength in D2 MSNs in dorsolateral striatum (DLS), suggesting similar cell-type-specific synaptic changes may underlie the development of habitual cocaine-seeking behavior. However, cell-type-specific synaptic changes have not been evaluated in DLS in this context. Therefore, we trained rats to self-administer cocaine in a cocaine self-administration paradigm that allows for differentiation of goal-directed vs. habitual cocaine-seeking behavior. Moreover, we used a viral vector under a D2-specific promoter to fluorescently label D2 MSNs with eYFP in DLS. Evoked excitatory postsynaptic currents (EPSCs) were used to determine AMPA:NMDA receptor ratio and the rectification index. Surprisingly, we did not observe any significant differences in these measures in DLS of cocaine-seeking rats, regardless of whether cocaine seeking was under habitual control. Interestingly, preliminary observations revealed significant changes in the paired pulse ratio (PPR), suggesting that presynaptic mechanisms may be involved in the development of habitual control over cocaine seeking. Overall, however, these results suggest there are no changes in postsynaptic strength of D2 MSNs in the DLS of rats with an extended history of cocaine self-administration and regardless of whether the cocaine seeking is under goal-directed or habitual control. Significance StatementThe study of drug abuse and drug addiction represents a critical area of research with significant public health implications. Importantly, the underlying neurobiology of the transition between drug abuse and drug addiction is not well understood and insights to this transition may aid in the development of novel treatment options. Behaviorally, the shift from goal-directed to habitual control is thought to underly this transition. Much is known about the neurobiology of goal-directed and habitual behavior, however the transition in the context of drug-seeking is not well defined. We observed no significant differences in measures of synaptic strength, suggesting such postsynaptic neuroplasticity in the dorsolateral striatum is not involved in this transition.