Microglial TNF-α Suppresses Cocaine-Induced Plasticity and Behavioral Sensitization.

ABSTRACT: Repeated administration of cocaine results in the development of behavioral sensitization, accompanied by a decrease in excitatory synaptic strength in the nucleus accumbens (NAc) through an unknown mechanism. Furthermore, glial cells in the NAc are activated by drugs of abuse, but the contribution of glia to the development of addictive behaviors is unknown. Tumor necrosis factor alpha (TNF-α), an inflammatory cytokine released by activated glia, can drive the internalization of synaptic AMPA receptors on striatal medium spiny neurons. Here we show that repeated administration of cocaine activates striatal microglia and induces TNF-α production, which in turn depresses glutamatergic synaptic strength in the NAc core and limits the development of behavioral sensitization. Critically, follo

SUBMITTER: Lewitus GM 

PROVIDER: S-EPMC4860141 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature