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Tipping the Scales Toward Addiction

      Despite diverse acute pharmacological actions, all drugs of abuse produce many similar behaviors, such as psychomotor sensitization, conditioned drug taking, drug seeking, and relapse (
      • Nestler E.J.
      Is there a common molecular pathway for addiction?.
      ). The development of these addiction-related behaviors is thought to arise from diverse molecular and cellular adaptations, which collectively result in convergent long-term functional alterations of the striatum. However, at the cellular level, on the one hand, exposure to different classes of drugs, such as stimulants versus opioids (
      • Russo S.J.
      • Dietz D.M.
      • Dumitriu D.
      • Morrison J.H.
      • Malenka R.C.
      • Nestler E.J.
      The addicted synapse: Mechanisms of synaptic and structural plasticity in nucleus accumbens.
      ), induces distinct and often opposing forms of adaptations in striatal medium spiny neurons (MSNs). On the other hand, exposure to alcohol promotes alcohol consumption by simultaneously activating both excitatory and inhibitory synaptic signaling, two seemingly opposing mechanisms, in the striatum (
      • Wang J.
      • Lanfranco M.F.
      • Gibb S.L.
      • Yowell Q.V.
      • Carnicella S.
      • Ron D.
      Long-lasting adaptations of the NR2B-containing NMDA receptors in the dorsomedial striatum play a crucial role in alcohol consumption and relapse.
      ,
      • Nie H.
      • Rewal M.
      • Gill T.M.
      • Ron D.
      • Janak P.H.
      Extrasynaptic delta-containing GABAA receptors in the nucleus accumbens dorsomedial shell contribute to alcohol intake.
      ). It remains underexplored how such opposing synaptic mechanisms contribute to the same behavioral states induced by drugs of abuse.
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      Linked Article

      • Distinct Synaptic Strengthening of the Striatal Direct and Indirect Pathways Drives Alcohol Consumption
        Biological PsychiatryVol. 81Issue 11
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          Repeated exposure to addictive drugs or alcohol triggers glutamatergic and gamma-aminobutyric acidergic (GABAergic) plasticity in many neuronal populations. The dorsomedial striatum (DMS), a brain region critically involved in addiction, contains medium spiny neurons (MSNs) expressing dopamine D1 or D2 receptors, which form direct and indirect pathways, respectively. It is unclear how alcohol-evoked plasticity in the DMS contributes to alcohol consumption in a cell type–specific manner.
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