====== Cocaine withdrawal ======


[[Cocaine]] [[withdrawal]] occurs when someone who has used a lot of [[cocaine]] cuts down or quits taking the [[drug]].
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Cocaine use followed by [[withdrawal]] induces [[synaptic plasticity]] in the [[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). 
Gupta et al. investigated the potential involvement of [[carbonic anhydrase]] 4 (CA4), an extracellular pH-buffering enzyme. 
They examined the effects of [[CA4]] in [[mice]] on ASIC-mediated synaptic transmission in [[medium spiny neuron]]s (MSNs) in NAc, as well as on cocaine-induced synaptic changes and behavior. 
They found that CA4 is expressed in the NAc and present in [[synaptosome]]s. Disrupting CA4 either globally, or locally, increased ASIC-mediated synaptic currents in NAc MSNs and protected against [[cocaine withdrawal]]-induced changes in [[synapse]]s and cocaine-seeking behavior. These findings raise the possibility that CA4 might be a previously unidentified therapeutic target for addiction and relapse
((Gupta SC, Ghobbeh A, Taugher-Hebl RJ, Fan R, Hardie JB, LaLumiere RT, Wemmie JA. Carbonic anhydrase 4 disruption decreases synaptic and behavioral adaptations induced by cocaine withdrawal. Sci Adv. 2022 Nov 18;8(46):eabq5058. doi: 10.1126/sciadv.abq5058. Epub 2022 Nov 16. PMID: 36383659.)).