| First Author | Gupta SC | Year | 2022 |
| Journal | Sci Adv | Volume | 8 |
| Issue | 46 | Pages | eabq5058 |
| PubMed ID | 36383659 | Mgi Jnum | J:331961 |
| Mgi Id | MGI:7397725 | Doi | 10.1126/sciadv.abq5058 |
| Citation | Gupta SC, et al. (2022) Carbonic anhydrase 4 disruption decreases synaptic and behavioral adaptations induced by cocaine withdrawal. Sci Adv 8(46):eabq5058 |
| abstractText | 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. |
