Sucrose intake: increase in non-stressed rats and reduction in chronically stressed rats are both prevented by the gamma-hydroxybutyrate (GHB) analogue, GET73.

It has been previously shown that the gamma-hydroxybutyrate analogue N-(4-trifluoromethylbenzyl)-4-methoxybutanamide (GET73) inhibits consumption and reinforcing effect of palatable food, in rats, at doses that have no detrimental effect on open-field behaviour. Here we show that GET73 is also able to prevent both the development of preference for a sucrose solution in non-stressed rats, and the reduction of preference for a sucrose solution induced by the daily exposure to continuously varied mildly stressful situations. Adult male Wistar Kyoto rats (180-190 g) were subjected to chronic unpredictable mild stress. Other rats of the same sex and strain were used to study the development of preference for a sucrose solution. Daily exposure to continuously varied mildly stressful situations produced a reduction of sucrose solution intake that started the 3rd week, and such reduction became highly significant during the 5th week. Treatment with GET73 (10 mg kg(-1), 50 mg kg(-1) or 100 mg kg(-1) once daily per os) produced a more evident reduction of sucrose solution intake during the 2nd and 3rd week, but during the 4th and 5th weeks the intake dose-dependently increased to values that, for the dose of 100 mg kg(-1), were not significantly different from those of non-stressed, vehicle-treated rats. In the same range of doses GET73 dose-dependently prevented the development of preference for a sucrose solution in non-stressed rats. The present data indicate that rats treated with GET73 do not develop the "depression-like" condition produced by the daily exposure, for several weeks, to continuously and unpredictably varied stressful situations in a valid (face, predictive, and construct validity) "depression" model. Moreover, GET73 prevents the development of preference for a sucrose solution in non-stressed rats. Concurrently, present and previous data suggest that GET73 "stabilize" the behaviour of rats, either preventing the development of a "depression-like" condition in a continuously stressful environment, or the rewarding effect of alcohol, sucrose, and palatable food.