Preference for palatable food is reduced by the gamma-hydroxybutyrate analogue GET73, in rats

Pharmacol Res. 2007 Apr;55(4):271-9. doi: 10.1016/j.phrs.2006.12.002. Epub 2006 Dec 19.

Abstract

Palatability and variety of foods are major reasons for "hedonic" eating, and hence for overeating and obesity. Palatable food and drugs of abuse share a common reward mechanism, and compounds that block the reinforcing effect of drugs of abuse preferentially suppress the intake of palatable foods. This research was aimed at studying the influence of the gamma-hydroxybutyrate analogue N-(4-trifluoromethylbenzyl)-4-methoxybutanamide (GET73) - that inhibits alcohol consumption - on consumption and reinforcing effect of palatable food. Adult male rats were used. For place preference conditioning, sweetened corn flakes were used as the reinforcer, and GET73 (50, 100 and 200mgkg(-1)) or vehicle were orally (p.o.) administered either 30min before each training session and the test session, or only before the test session. To study the influence on consumption, GET73 was given p.o. at the same doses once daily for 12 days to rats given free access to both palatable and varied food (cafeteria diet) or to standard chow. Both acquisition and expression of palatable food-induced conditioned place preference were inhibited by GET73, either administered throughout the conditioning period or only before the test session. GET73 reduced also the consumption of cafeteria food, while that of standard chow was increased. At these doses, GET73 had no detrimental effect on open-field behaviour. GET73 seems to specifically attenuate the gratification produced by varied and palatable food, without affecting the consumption of not particularly palatable chow. Since, overweight and obesity are mostly due to the overeating of palatable and varied foods, drugs like GET73 could represent a somewhat ideal and rational approach to obesity treatment.

MeSH terms

  • Anilides / pharmacology*
  • Animals
  • Anti-Obesity Agents / pharmacology*
  • Behavior, Animal / drug effects*
  • Conditioning, Psychological / drug effects
  • Dose-Response Relationship, Drug
  • Food Preferences / drug effects*
  • Male
  • Motor Activity / drug effects
  • Rats
  • Rats, Wistar
  • Reinforcement Schedule
  • Reinforcement, Psychology*
  • Reward
  • Taste*

Substances

  • Anilides
  • Anti-Obesity Agents
  • N-(4-trifluoromethylbenzyl)-4-methoxybutanamide