Microglial TNF-α Suppresses Cocaine-Induced Plasticity and Behavioral Sensitization
| Autor: | Keanan Augereau, Gil M. Lewitus, David Stellwagen, Horia Pribiag, Sarah C. Konefal, Andrew D. Greenhalgh |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
AMPA receptor Motor Activity Neurotransmission Nucleus accumbens Medium spiny neuron Receptors N-Methyl-D-Aspartate Synaptic Transmission Article Nucleus Accumbens Rats Sprague-Dawley Cocaine-Related Disorders 03 medical and health sciences Glutamatergic 0302 clinical medicine Cocaine medicine Animals Receptors AMPA Sensitization Neuronal Plasticity Behavior Animal Microglia Tumor Necrosis Factor-alpha Chemistry General Neuroscience Behavior Addictive 030104 developmental biology medicine.anatomical_structure nervous system Excitatory postsynaptic potential Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | Lewitus, G, Konefal, S, Greenhalgh, A, Pribiag, H, Augereau, K & Stellwagen, D 2016, ' Microglial TNF-α Suppresses Cocaine-Induced Plasticity and Behavioral Sensitization ', Neuron, vol. 90, no. 3, pp. 483-491 . https://doi.org/10.1016/j.neuron.2016.03.030 |
| DOI: | 10.1016/j.neuron.2016.03.030 |
| Popis: | 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, following a period of abstinence, a weak TLR4 agonist can reactivate microglia, increase TNF-α production, depress striatal synaptic strength, and suppress cocaine-induced sensitization. Thus, cytokine signaling from microglia can regulate both the induction and expression of drug-induced behaviors. |
| Databáze: | OpenAIRE |
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