Dietary modulation of the anorectic potency of amphetamine

The effects of intake of an amphetamine solution on food and fluid intakes, body weight (b.wt.) and feed efficiency (FE) were examined in rats fed either a high-carbohydrate (HC) (65% of total calories) or high-fat (HF) (65% of total calories) diet. During a 17-day predrug period, neither caloric intake, fluid intake, b.wt. nor feed efficiency (FE) differed as a function of diet. When given a 0.1 mg/ml amphetamine sulfate (AMPH) solution as their sole source of fluid, rats in both diet groups decreased fluid intake by an equivalent amount. While diet did not influence AMPH intake, it did alter the drug's effects on caloric intake, b.wt. and FE. In both diet groups, rats drinking AMPH decreased caloric intake, b.wt. gain and FE relative to rats which drank water. However, rats fed the HC diet decreased caloric intake less, but lost more weight than rats fed the HF diet. Further, rats fed the HC diet displayed a rapid tolerance to the anorectic effects of AMPH, with no tolerance to the drug's effect on b.wt. In contrast, rats fed the HF diet suppressed caloric intake throughout the drug period, but weighed more than rats fed the HC diet. Thus, when drinking the AMPH solution, FE of rats fed the HC diet was significantly lower than that of rats fed the HF diet. When the drug was removed, rats eating the HC diet failed to alter caloric intake and b.wt. In contrast, rats fed the HF diet increased caloric intake and gained weight. These data indicate that dietary factors must be considered when evaluating the anorectic actions of psychopharmacological agents.