The interaction between Environmental Enrichment and fluoxetine in inhibiting sucrose-seeking renewal in mice depend on social living condition

Rationale: Several single or combined therapeutic approaches have been developed to treat addiction, however with partial efficacy in preventing relapse. Recently, the living environment has been suggested as a critical intervening factor determining the treatment outcomes. Despite accumulating evidence confirming a role of living conditions in the vulnerability to addictive behaviours, their impact on single or integrative therapeutic strategies preventing relapse is yet to be identified. Objectives: Here, we explore the possible interaction between brief Environmental Enrichment (EE) exposure and acute fluoxetine administration in inhibiting sucrose-seeking behaviours, and whether this effect could be affected by living environment. Methods: Social and isolated adult male C57BL/6 mice were trained to sucrose self-administration associated to a specific conditioning context (CxA), followed by a 7-day extinction in a different context (CxB). Afterwards, mice were exposed for 22 h to EE and then injected with fluoxetine (10 mg/kg, i.p.) 1 h before a CxA-induced sucrose-seeking test. Results: Brief EE exposure and acute fluoxetine administration alone inhibited context-induced sucrose-seeking in both housing conditions; however, they exhibited additive properties only in social condition. Conclusions: Our data show that social environment may influence the EE/fluoxetine interaction in inhibiting relapse to sucrose. These findings suggest that setting up proper living conditions to boost the efficacy of therapeutic approaches may represent a fundamental strategy to treat addiction disorders.