{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T19:46:14Z","timestamp":1768506374603,"version":"3.49.0"},"posted":{"date-parts":[[2023,5,22]]},"group-title":"Neuroscience","reference-count":68,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,5,22]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  The increasing rates of drug misuse highlight the urgency of identifying improved therapeutics for treatment. Most drug-seeking behaviors that can be modeled in rodents utilize the repeated intravenous self-administration (SA) of drugs. Recent studies examining the mesolimbic pathway suggest that K\n                  <jats:sub>v<\/jats:sub>\n                  7\/KCNQ channels may contribute in the transition from recreational to chronic drug use. However, to date, all such studies used noncontingent, experimenter-delivered drug model systems, and the extent to which this effect generalizes to rats trained to self-administer drug is not known. Here, we tested the ability of retigabine (ezogabine), a K\n                  <jats:sub>v<\/jats:sub>\n                  7 channel opener, to regulate instrumental behavior in male Sprague Dawley rats. We first validated the ability of retigabine to target experimenter-delivered cocaine in a CPP assay and found that retigabine reduced the acquisition of place preference. Next, we trained rats for cocaine-SA under a fixed-ratio or progressive-ratio reinforcement schedule and found that retigabine-pretreatment attenuated the self-administration of low to moderate doses of cocaine. This was not observed in parallel experiments, with rats self-administering sucrose, a natural reward. Compared to sucrose-SA, cocaine-SA was associated with reductions in the expression of the K\n                  <jats:sub>v<\/jats:sub>\n                  7.5 subunit in the nucleus accumbens, without alterations in K\n                  <jats:sub>v<\/jats:sub>\n                  7.2 and K\n                  <jats:sub>v<\/jats:sub>\n                  7.3. Therefore, these studies reveal a reward specific reduction in SA behavior considered relevant for the study of long-term compulsive-like behavior and supports the notion that K\n                  <jats:sub>v<\/jats:sub>\n                  7 is a potential therapeutic target for human psychiatric diseases with dysfunctional reward circuitry.\n                <\/jats:p>","DOI":"10.1101\/2023.05.18.541208","type":"posted-content","created":{"date-parts":[[2023,5,22]],"date-time":"2023-05-22T15:50:18Z","timestamp":1684770618000},"source":"Crossref","is-referenced-by-count":0,"title":["K\n                  <sub>v<\/sub>\n                  7 Channel Opener Retigabine Reduces Self-Administration of Cocaine but Not Sucrose in Rats"],"prefix":"10.64898","author":[{"given":"Esteban S.","family":"Urena","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cody C.","family":"Diezel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mauricio","family":"Serna","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Grace","family":"Hala\u2019ufia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisa","family":"Majuta","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kara R.","family":"Barber","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Todd W.","family":"Vanderah","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7758-4436","authenticated-orcid":false,"given":"Arthur 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