Although the importance of astrocyte energy metabolism in supporting synaptic neurotransmission and synaptic plasticity has been demonstrated, there is no data for the contribution of astrocyte mitochondria bioenergetics to opiate-induced plasticity. We propose to investigate the role for astrocyte mitochondria oxidative phosphorylation in heroin-induced plasticity. Specific Aim1 will identify the role for astrocyte mitochondria oxidative phosphorylation in mediating heroin-induced plasticity. We hypothesize that knockdown of the Cox10 gene in NAc astrocytes will significantly increase cue- and/or drug-induced heroin seeking behavior in mice. Specific Aim 2 will determine the changes in oxidative phosphorylation, glycolytic activity and other relevant energy metabolism pathways in NAc astrocytes in wild-type mice during abstinence following heroin self-administration. We hypothesize that long-term abstinence following heroine intake leads to up-regulation of astrocyte energy metabolism pathways to result in heroin-induced plasticity. This innovative proposal will identify new astrocyte-specific metabolic pathways essential to the neurobiology underlying opioid addiction and relapse.