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CVT‐10216 selectively suppresses binge eating of palatable foods and attenuates dopamine release in the accumbens of rats
Author(s) -
Bocarsly Miriam E,
Aveicole M,
Hoebel Bartley G,
Paredes Daniel,
Arolfo Maria P,
Yao Lina,
Fan Peidong,
Diamond Ivan
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.1012.3
Subject(s) - nucleus accumbens , binge eating , chemistry , medicine , endocrinology , sucrose , microdialysis , dietary sucrose , dopamine , biochemistry , obesity
CVT‐10216 is a highly selective, reversible inhibitor of ALDH‐2 that reduces alcohol and cocaine intake in rats. Given overlaps in behavior and neurochemistry seen with binge eating and drug use, we examined the effects of CVT‐10216 on binge eating of palatable foods and subsequent dopamine (DA) release in the nucleus accumbens (NAc). Male Sprague‐Dawley rats (n=12/group) were maintained on 1) a binge schedule (12‐h deprivation then 12‐h access to chow and a 10% sucrose solution or vegetable shortening), 2) ad libitum chow with sucrose or shortening, or 3) only chow. After 25 days, CVT‐10216 (0, 7.5, or 15 mg/kg, i.p.) was administered. The 15 mg/kg dose decreased 1 h shortening and chow intake in binge eating rats (p<0.05) and decreased 24 h shortening intake in both the binge and ad libitum groups (p<0.05). This dose selectively decreased 1 h and 24 h intake of sugar in the sugar binge‐eating group (p<0.05). There was a slight decrease in 1 h chow intake for the ad libitum chow control group (p<0.05), but no effect on 24 h intake. In vivo microdialysis was performed in a new set of rats (n=8/group) fed binge sucrose or ad libitum sucrose and chow. CVT‐10216 (15 mg/kg) attenuated the rise in extracellular DA levels in rats binge eating sucrose (p<0.05). These preclinical findings suggest that selective, reversible ALDH‐2 inhibitors may have therapeutic potential to reduce binge eating behavior in clinical populations. Grant Funding Source : Gilead Sciences