ACETAZOLAMIDE INCREASES LOCOMOTION, EXPLORATORY BEHAVIOR, AND WEIGHT LOSS FOLLOWING SOCIAL STRESS: A TREATMENT FOR EMOTIONAL EATING?

Background Amphetamines and sympathomimetics (e.g. phenylpropanolamine and ephedrine) are effective, centrally acting drugs that induce weight loss through their potent anorexic and locomotor properties. We first reported that amphetamines and these sympathomimetic agents antagonize catecholamine‐dependent, alpha‐2 adrenergic receptor‐dependent signal transduction mediated by chloride/bicarbonate transport. Hypothesis Other drugs that target and inhibit cellular bicarbonate/chloride antiport would similarly demonstrate anorectic properties, induce locomotion, and diminish weight gain ‐‐especially in disorders such as depression or social isolation where there is an increase in emotional eating. Methods Male and female inbred mice were housed in groups or they underwent the stress of living in social isolation or in solitary metabolic chambers for five days. Mice consumed either normal rodent chow or a rodent food supplemented with high fat, high fructose corn syrup; water was provided ad libitum. To inhibit chloride/bicarbonate transport, acetazolamide (ACT, 3 mM) or vehicle was added to the drinking water. There were no noticeable adverse effects in mice receiving ACT. Following a period of habituation, rodents underwent evaluations of exploratory locomotion and learning with the object recognition test. Food intake and weights were also tracked; for all groups, n ≥ 9. Results Compared to the control, unstressed, group housed rodents, living in social isolation reduced spontaneous exploration time in male mice (values expressed as means in sec ± SEM) from 23 ± 4 to 14 ± 3 (p<0.001), and in female mice, from 47 ± 6 to 23 ± 3 (p<0.001). Drinking water supplemented with ACT had no effect on exploration time in group housed mice, but ACT completely restored the diminished exploration time found in mice stressed by isolation to control, grouped mice values. The ratio of time spent exploring new objects compared to familiar items (DR ratio) was also reduced following social isolation from 2.6 ± 0.5 to 1.2 ± 0.2 (p<0.001). ACT completely normalized the DR ratio of the stressed mice. The body weight of female mice fed high fat, high fructose corn syrup diets for 12 weeks and given ACT was significantly reduced when compared to mice drinking only water (weight in g ± SEM), 23.7 + 0.8 v. 21.0 + 0.5, p=0.02. This difference in weight was not due to changes in body water volume, but instead, due to the significant decrease in food consumption and greater locomotor activity recorded in mice fed the ACT. Conclusion Drugs that inhibit chloride/bicarbonate transport could offer a safe, new approach to achieving behavioral weight loss in obese individuals with emotional eating. Support or Funding Information University of Missouri This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .