Behavioural and Brain Mechanisms of Sustained Contingency Degradation

titleBehavioural and Brain Mechanisms of Sustained Contingency Degradation
start_date2024/04/17
schedule14h
onlineno
location_info/
summaryPreclinical models of treatments for substance use disorder have typically involved extinction, during which once-rewarded cues or actions are no longer paired with reward. One problem with extinction, however, is that extinguished responding tends to spontaneously recover over time. We therefore tested whether contingency degradation might be effective in producing a reduction in responding that does not spontaneously recover. In Experiment 1, rats were trained to press a left lever for pellets and a right lever for a sucrose solution, or the opposite arrangement, counterbalanced. Following training, although both levers continued to earn their respective outcomes, one of outcomes was also delivered when no lever press had occurred. This degraded the contingency between that lever and its outcome, because rats selectively reduced responding on that lever. When given a 10 min test in which both levers were extended and no outcomes delivered, rats responded in accordance with the degradation contingencies (i.e. NonDegraded > Degraded) regardless of whether they were tested 1 day or 2 weeks after degradation, suggesting that degradation does not spontaneously recover. In Experiment 2, we investigated whether chemogenetically inhibiting glutamatergic neurons in the lateral OFC impaired degradation learning using this paradigm. Animals injected with the control virus (mCitrine+DCZ group) learned degradation, whereas animals for whom the lateral OFC was inhibited prior to degradation training (hM4Di+DCZ group) did not (i.e. nondegraded = degraded), and this pattern of results was retained at both immediate and delayed tests. A third experiment will determine whether this sustained impairment in extinction will persist when the lateral OFC is chemogenetically silenced during test. Together, these experiments suggest that the behavioural and brain mechanisms of contingency degradation and extinction are distinct, and that degradation is more effective in producing a lasting behavioural change.
responsiblesPerrais, Thoumine