Publication
Outcome-selective reinstatement is predominantly context-independent, and associated with c-Fos activation in the posterior dorsomedial striatum
Publisher:
Cold Spring Harbor Laboratory
Date:
29-07-2021
DOI:
10.1101/2021.07.28.454246
Abstract: Research from human and animal studies has found that responding that has been successfully reduced following treatment can return upon exposure to certain contexts. An in idual in recovery from alcohol use disorder, for ex le, might relapse to drinking upon visiting their favourite bar. However, most of these data have been derived from experiments involving a single (active) response, and the context-dependence of returned responding in situations involving choice between multiple actions and outcomes is less well-understood. We thus investigated how outcome-selective reinstatement – a procedure 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. Reinstatement testing consisted of one food outcome being delivered ‘freely’ (i.e. unearned by lever pressing and unsignalled by cues) to the food magazine every 4 minutes in the following order: Sucrose, Pellet, Pellet, Sucrose. Selective reinstatement was considered intact if pellet delivery increased pressing selectively on the pellet lever, and sucrose delivery selectively increased pressing on the sucrose 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 predominantly context-independent, and that intact reinstatement is related to neuronal activity in the pDMS. Outcome-selective reinstatement is predominantly context-independent Outcome-selective reinstatement is entirely context-independent after multiple extinction sessions Outcome-selective reinstatement increases c-Fos expression in dorsomedial striatum c-Fos expression in orbitofrontal cortex and dorsal hippoc us is unaffected by selective reinstatement.