Abstract
Repeated cocaine administration produces enduring molecular, cellular and behavioral plasticity which is associated with changes in striatal glutamatergic neurotransmitter system, as well as with increases in pro-inflammatory cytokines such as TNF-alpha. Recently, we have reported that TNF-alpha, a cytokine expressed in the CNS by glia, can drive the internalization of synaptic AMPA receptors on striatal medium spiny neurons. Furthermore, glial cells in the striatum are activated by a variety of drugs of abuse, but the contribution of glia to the development of addictive behaviors is unknown. The aim of the present study is to investigate the role of TNF-alpha on the straital plasticity induced by cocaine. We found that chronic administration of cocaine specifically activates striatal microglia and induces TNF-alpha production, which in turn depresses glutamatergic synaptic strength in the NAc core and limits the development of behavioral sensitization. Furthermore, we found that activation of microglia by a weak TLR4 agonist depresses striatal synaptic strength and suppresses cocaine-induced sensitization. Thus, manipulating microglia to boost TNF-alpha is a potential avenue for the treatment of addiction.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
