Dopamine ligands and the stimulus effects of amphetamine: animal models versus human laboratory data
The interaction between the receptor antagonist thymoxamine (THYM), propranolol (PPL) and metergoline (MTG) with dexamphetamine (d-Amp)-induced anorexia was examined in a series of studies in normal female volunteers. Visual analogue scale (VAS) ratings of hunger were made and food intake was measured using an automated solid food dispenser (AFD). d-Amp (10 mg) significantly depressed hunger ratings compared to placebo in two of the three studies and its effect was countered by the addition of MTG (4 mg). d-Amp significantly reduced food intake compared to placebo in two studies. In all trials the reduction in food intake following d-Amp was significantly greater than would have been predicted from its effect on hunger. THYM (160 mg) and PPL (40 mg) were associated with no changes in food intake when given alone or with d-Amp, MTG increased food intake (but not significantly) and the combined effects of MTG and d-Amp was the algebraic sum of the effect of each; but there appeared to be no true pharmacological interaction between blocker and anorectic. The results indicated that there may be some dissociation between the effect of d-Amp on hunger and food intake but have failed to produce evidence that noradrenergic pathways are involved. The results are consistent with the theories that d-Amp anorexia does not involve the release of 5-hydroxytryptamine (5-HT) but that 5-HT pathways are involved in the feeding process.