Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cocaine / pharmacology*
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Conditioning, Operant / drug effects
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Conditioning, Operant / physiology
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Dopamine Uptake Inhibitors / pharmacology*
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Electric Stimulation
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Excitatory Postsynaptic Potentials / drug effects
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Excitatory Postsynaptic Potentials / physiology
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Green Fluorescent Proteins / genetics
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Green Fluorescent Proteins / metabolism
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Habenula / cytology
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Habenula / drug effects*
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Habenula / metabolism
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Hindlimb Suspension
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In Vitro Techniques
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Luminescent Proteins / genetics
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Luminescent Proteins / metabolism
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Mice
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Mice, Inbred C57BL
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Mice, Transgenic
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Motor Activity / drug effects
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Mutation / genetics
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Patch-Clamp Techniques
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Protein Transport / drug effects*
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Receptors, AMPA / genetics
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Receptors, AMPA / metabolism*
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Red Fluorescent Protein
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Swimming / psychology
Substances
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Dopamine Uptake Inhibitors
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Luminescent Proteins
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Receptors, AMPA
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Green Fluorescent Proteins
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Cocaine
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glutamate receptor ionotropic, AMPA 1