期刊
SCIENCE ADVANCES
卷 8, 期 46, 页码 -出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciadv.abq5058
关键词
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资金
- National Institute of Drug Abuse [R01DA052953, 5R01DA037216]
- Department of Veterans Affairs [IO1BX004440]
- Roy J. Carver Charitable Trust
- [DA049139]
- [DA048055]
The study finds that carbonic anhydrase 4 (CA4) plays an important role in cocaine addiction, as disrupting CA4 can increase ASIC-mediated synaptic currents in the nucleus accumbens (NAc), protecting against cocaine withdrawal-induced synaptic changes and cocaine-seeking behavior.
Cocaine use followed by withdrawal induces synaptic changes in nucleus accumbens (NAc), which are thought to underlie subsequent drug-seeking behaviors and relapse. Previous studies suggest that cocaine-induced synaptic changes depend on acid-sensing ion channels (ASICs). Here, we investigated potential involvement of carbonic anhydrase 4 (CA4), an extracellular pH-buffering enzyme. We examined effects of CA4 in mice on ASIC-mediated synaptic transmission in medium spiny neurons (MSNs) in NAc, as well as on cocaine-induced synaptic changes and behavior. We found that CA4 is expressed in the NAc and present in synaptosomes. Disrupting CA4 either globally, or locally, increased ASIC-mediated synaptic currents in NAc MSNs and protected against cocaine withdrawal-induced changes in synapses and cocaine-seeking behavior. These findings raise the possibility that CA4 might be a previously unidentified therapeutic target for addiction and relapse.
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