Optogenetic control of alcohol-seeking behavior via the dorsomedial striatal circuit
| Autor: | Xiaowen Zhuang, Jun Wang, E. K. Williams, Bradley Jones, Tengfei Ma, Jiayi Lu, Swetha Jayavelu, Annalise Binette, Emily A. Roltsch Hellard |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Male Alcohol Drinking Drug-Seeking Behavior Self Administration Alcohol use disorder Optogenetics Medium spiny neuron Article 03 medical and health sciences Cellular and Molecular Neuroscience Glutamatergic 0302 clinical medicine Dopamine receptor D2 medicine Animals Direct pathway of movement Rats Long-Evans Pharmacology Ethanol Chemistry medicine.disease Corpus Striatum Rats 030104 developmental biology Dopamine receptor NMDA receptor Conditioning Operant Nerve Net Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | Neuropharmacology |
| ISSN: | 1873-7064 |
| Popis: | Alcohol consumption alters glutamatergic transmission in many brain regions, including the dorsomedial striatum (DMS); this aberrant plasticity is thought to be responsible for alcohol-seeking behavior. Recent studies reported that alcohol induced such plasticity specifically in direct pathway spiny projection neurons (dSPNs) of the DMS. However, it is unknown how this specific change contributes to alcohol-seeking behavior and relapse. Here, we first demonstrated that operant alcohol self-administration increased NMDA receptor activity in DMS dSPNs. Next, we found that optogenetic inhibition of dSPNs reversibly decreased operant lever presses for alcohol and alcohol intake. Furthermore, optogenetic stimulation of corticostriatal inputs at low and moderate frequencies induced reliable LTD in DMS slices. Surprisingly, in vivo delivery of the LTD-inducing protocol increased operant alcohol self-administration; this effect was blocked by a D2R antagonist. Importantly, LTD induction in the presence of both D1 and D2 receptor antagonists produced a long-lasting decrease in operant alcohol self-administration. Our results suggest that suppressing DMS dSPNs activity and their cortical inputs represents a novel treatment mechanism for alcohol use disorder. |
| Databáze: | OpenAIRE |
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