Environmental enrichment selectively counteracts brain metabolic activity during cocaine abstinence

Environmental enrichment (EE) is a promising strategy to promote recovery from addiction, but its neurobiological mechanisms remain poorly understood. In this study we used 18-fluorodeoxyglucose (FDG) microPET imaging to investigate how exposure to EE during abstinence affects brain neuroadaptations induced by voluntary intake of cocaine at different time of abstinence. After establishing escalated cocaine intake, male rats were housed in enriched or standard environments for four weeks and their brain metabolic activity was assessed after one and four weeks of abstinence. Cocaine self-administration produced widespread decreases in cortical metabolic activity, particularly in regions involved in executive function (orbitofrontal cortex, anterior cingulate), interoception (insula) and motivation (nucleus accumbens), while increasing activity in emotional circuits (ventral hippocampus) and the mesencephalon. EE selectively normalized these alterations restoring nucleus accumbens and orbitofrontal cortex activity. These findings reveal circuit-specific effects of environmental enrichment on cocaine-induced brain adaptations and suggest that effective addiction treatment requires both early interventions targeting reward circuits and sustained environmental stimulation to restore executive function, potentially reducing both immediate craving intensity and long-term relapse vulnerability.