Outcome-selective reinstatement is partially context-dependent, and associated with c-Fos activation in the posterior dorsomedial striatum

Research from human and animal studies has found that relapse to compulsive action can be provoked by exposure to certain contexts. However, most of these data have been derived from experiments involving a single active response, and the context-specificity of relapse in situations involving choice between multiple actions and outcomes is less well-understood. We thus investigated how outcome-selective reinstatement involving choice between multiple actions was affected by altering the physical context in rats. In Experiment 1, rats were trained over 6 days to press a left lever for one food outcome (pellets or sucrose) and a right lever for the other outcome. Then, rats received an extinction session in either the same context (A) as lever press training, or in a different context (B). Rats were tested immediately (5 minutes) after extinction in Context A or B such that there were four groups in total: AAA, ABB, ABA, and AAB. Testing consisted of unsignalled presentations of pellet and sucrose outcomes, and selective reinstatement was intact if these presentations reinstated responding on the same lever that earned the outcome during training, e.g. pellet delivery should reinstate responding on the pellet lever. This result (Reinstated > Nonreinstated) was observed for rats in group AAA and ABB, but not rats in groups ABA and AAB. Experiment 2 was conducted identically, except that rats received two extinction sessions over two days and tested one day later. This time, all groups demonstrated intact outcome-selective reinstatement regardless of context. Analysis of c-Fos expression in several brain regions revealed that only c-Fos expression in the posterior dorsomedial striatum (pDMS) was related to intact reinstatement performance. Overall, these results suggest that outcome-selective reinstatement is partially context-dependent, and that intact reinstatement is related to neuronal activity in the pDMS. HighlightsO_LIOutcome-selective reinstatement is partially context-dependent C_LIO_LIOutcome-selective reinstatement is entirely context-independent after multiple extinction sessions C_LIO_LIOutcome-selective reinstatement increases c-Fos expression in dorsomedial striatum C_LIO_LIc-Fos expression in orbitofrontal cortex and dorsal hippocampus is unaffected by selective reinstatement. C_LI