Genetic and pharmacological amelioration of mitochondrial dysfunction in VTA alleviate the development of opiate-dependence

Converging studies have shown that the dysfunction in VTA neuronal ensembles in during chronic opioid analgesics administration. However, the hub dysregulated signal pathways in VTA functional ensembles, which mediating opioid tolerance and the negative affect, and the therapeutic targeting strategies, remain unclear. Here, we used Cre-dependent Tet-Off system to label and temporary control dopaminergic neuronal ensembles recruited by initial morphine exposure. Single-cell RNA-seq in these neurons revealed the dysregulation of mitochondrial respiratory and mitophagy signal pathways following chronic morphine administration.