Priority CommunicationChlorzoxazone, an SK-Type Potassium Channel Activator Used in Humans, Reduces Excessive Alcohol Intake in Rats
Section snippets
Alcohol Self-Administration
Adult male Wistar rats (250–275 g, Harlan, Livermore, California) drank 20% alcohol or water under a two-bottle choice, home-cage, IAA paradigm modified from Simms et al. (12). Rats had 24-hour access to alcohol 3 days/week (starting Monday, Wednesday, and Friday) for 5–6 weeks. Rats were then switched to only 3-hour access to alcohol on the 3 days/week to simplify detection of CZX-related intake changes. After 5–6 weeks of 3-hour/day, 3-day/week IAA drinking, the effects of CZX were examined.
Results
As shown in Figure 1, IAA rats were trained to drink 20% alcohol versus water under a two-bottle choice, home-cage, intermittent access to alcohol paradigm, whereas CAA rats had continuous access to 20% alcohol concurrent with water. Chlorzoxazone significantly and dose-dependently reduced alcohol drinking in IAA rats, determined after 3 hours access to alcohol (Figure 2A) [F(3,74) = 17.45, p < .001] or 1 hour access to alcohol (Figure 2C) [F(3,74) = 20.63, p < .001]. Importantly, CZX did not
Discussion
The present study demonstrates that CZX, an FDA-approved SK activator (10) used for decades in humans as a centrally acting myorelaxant (11), reduced excessive alcohol intake in IAA rats but not moderate alcohol intake in CAA rats. CZX significantly and dose-dependently decreased alcohol intake in IAA rats, with no effect on concurrent water intake. In contrast, CZX did not reduce alcohol or water intake in CAA rats; the lack of effect of CZX in CAA rats was not due to a floor effect, because
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2015, Carbohydrate PolymersCitation Excerpt :CZX has been proven to present certain curative effects on systemic mastocytosis, conjunctivitis, and ulcerative colitis (Gnanasambandan, Gunasekaran, & Seshadri, 2014); it can also be used to treat children's mental dysplasia caused by central nervous system lesions. Several researchers have reported a number of CZX applications (Feil et al., 2013; Hopf et al., 2011; Shaik & Mehvar, 2011). Despite the many benefits of the drug, the biomedical applications of CZX are still limited by its disadvantages, which include low water solubility and high toxicity.