Abstract # 1765 Microglia suppress cocaine-induced plasticity and behavioral sensitization trough TNF-alpha

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...

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Veröffentlicht in:Brain, behavior, and immunity behavior, and immunity, 2016-10, Vol.57, p.e17-e17
Hauptverfasser: Lewitus, G.M, Konefal, S.C, Greenhalgh, A.D, Pribiag, H, Stellwagen, D
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Sprache:eng
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Zusammenfassung: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.
ISSN:0889-1591
1090-2139
DOI:10.1016/j.bbi.2016.07.058