Journal article
Carbonic anhydrase 4 disruption decreases synaptic and behavioral adaptations induced by cocaine withdrawal
Science advances, Vol.8(46), pp.eabq5058-eabq5058
11/18/2022
DOI: 10.1126/sciadv.abq5058
PMCID: PMC9668291
PMID: 36383659
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.
Details
- Title: Subtitle
- Carbonic anhydrase 4 disruption decreases synaptic and behavioral adaptations induced by cocaine withdrawal
- Creators
- Subhash C GuptaAli GhobbehRebecca J Taugher-HeblRong FanJason B HardieRyan T LaLumiereJohn A Wemmie
- Resource Type
- Journal article
- Publication Details
- Science advances, Vol.8(46), pp.eabq5058-eabq5058
- DOI
- 10.1126/sciadv.abq5058
- PMID
- 36383659
- PMCID
- PMC9668291
- NLM abbreviation
- Sci Adv
- eISSN
- 2375-2548
- Language
- English
- Date published
- 11/18/2022
- Academic Unit
- Molecular Physiology and Biophysics; Psychiatry; Psychological and Brain Sciences; Iowa Neuroscience Institute; Biology; Neurosurgery
- Record Identifier
- 9984315560902771
Metrics
14 Record Views