Effect of a serotonin 1-A agonist on food intake of Osborne-Mendel and S5B/P1 rats.

The effect on food intake of 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), a serotonin 1-A agonist, has been evaluated in two strains of rats that differ in their sensitivity to becoming obese while eating a high-fat diet. Male Osborne-Mendel (OM) and S5B/Pl rats were tested at 8 weeks and 16 weeks of age. Both strains were adapted to choose between two diets-a 56% fat energy diet, and a 10% fat energy diet-which were equicaloric for protein (24% energy). Daily food intake was measured for 2 weeks before injection of 8-OH-DPAT. The younger OM rats had no diet preference, while the older OM rats preferred the high-fat diet. The younger S5B/P1 rats preferred the low-fat diet, while the older S5B/P1 rats had no diet preference. Satiated rats were injected subcutaneously with 8-OH-DPAT at doses of 0.3, 1.0, or 3.0 mg/kg or vehicle. During the light phase, subcutaneous 8-OH-DPAT increased the intake of the high-fat diet in the 16-week-old OM rats but not the 8-week-old OM rats. 8-OH-DPAT had no effect on the low-fat diet intake in either age OM rat. The 8-week-old S5B/P1 rats showed a significant decrease in intake of the high-fat diet in response to 8-OH-DPAT, whereas an increase in the intake of the low-fat diet was observed in the older S5B/P1 rats. These data are consistent with the hypothesis that increased fat preference in Osborne-Mendel rats may result in part from altered serotonin activity of 5-HT(1A) receptors.