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

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Abstract

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.

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