Carbonic anhydrase 4 disruption decreases synaptic and behavioral adaptations induced by cocaine withdrawal.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 36383659.
- Also identified by DOI 10.1126/sciadv.abq5058 and PMC identifier 9668291.
- Licence recorded as CC BY-NC.
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Abstract
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.