Influence of benzodiazepines on body weight and food intake in obese and lean Zucker rats

1. The gamma-aminobutyric acid (GABA)-ergic system, which is functionally a ltered in obese (fa/fa) Zucker rats, plays an important; role in controllin g energy balance within the central nervous system. 2. GABA receptors seem to be involved in the dysfunction of the hypothalami c Energy homeostasis-controlling mechanisms in these animals due to a genet ically-induced defect of the leptin-neuropeptide Y system. 3. To shed further light on the possible role played by the GABA system in the pathogenesis of this rat model, two benzodiazepine (BDZ) receptor agoni sts (diazepam and clonazepam) and one BDZ antagonist (flumazenil) were admi nistered intraperitoneally in obese and lean Zucker rats, 4. Body weight: gain was reduced by the BDZ agonists in both phenotypes, an d one receptor-agonist (diazepam) lowered insulin concentration in obese ra ts. In GABA-antagonist-treated obese rats, the daily amount of body weight gain and food intake acquired an oscillatory rhythm similar to that of norm al rodents. 5. By demonstrating the role of BDZ receptors, these findings may help clar ify the pathophysiology of obesity and insulin resistance in fatty Zucker r ats.