Syracuse

Cocaine-evoked negative symptoms require AMPA receptor trafficking in the lateral habenula

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Meye, Frank, J | Valentinova, Kristina | Lecca, Salvatore | Marion-Poll, Lucile | Maroteaux, Matthieu, J | Musardo, Stefano | Moutkine, Imane | Gardoni, Fabrizio | Huganir, Richard, L | Georges, F | Mameli, Manuel

Edité par CCSD ; Nature Publishing Group -

International audience. Addictive substances mediate positive and negative states promoting persistent drug use. However, substrates for aversive effects of drugs remain elusive. We found that, in mouse lateral habenula (LHb) neurons targeting the rostromedial tegmental nucleus, cocaine enhanced glutamatergic transmission, reduced K + currents and increased excitability. GluA1 trafficking in LHb was instrumental for these cocaine-evoked modifications and drug-driven aversive behaviors. Altogether, our results suggest that long-lasting adaptations in LHb shape negative symptoms after drug taking. Withdrawal from addictive substances, including cocaine, produces negative symptoms such as a depressive-like phenotype that contributes to compulsive drug abuse 1,2. The lateral habenula (LHb) inhibits monoaminergic systems via the GABAergic rostromedial tegmental

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