Astrocyte energy metabolism in opiate use disorders

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.