Tolerance pattern to amphetamine anorexia after selective lesions in the hypothalamic dopaminergic projection

Tolerance to the anorexic effect of d-amphetamine was studied in rats with selective dopamine lesions in the forebrain by means of 6-hydroxy dopamine, and measuring the food intake during two consecutive 2 h periods. Lesions placed in the perifornical hypothalamus (PFH) strongly antagonised the anorexic effect, whereas, lesions produced via intraventricular injections affected the anorexia only marginally. Amphetamine anorexia observed in the first 2 h in control and lesioned groups remained persistently, without any evidence of tolerance, up to 2 weeks of treatment. The second 2 h food intake exhibited a progressive increase which contributed to the apparent tolerance seen in total 4 h food intake in the control and lesioned animals. The onset and completion of this apparent tolerance was markedly delayed in the dopamine depleted group; lesions placed in the relatively medial areas delayed the tolerance development more effectively than that of PFH lesions. The stimulant effect of amphetamine on locomotion was abolished in lesioned animals. The results indicate that an apparent tolerance to amphetamine anorexia still developed in animals with forebrain dopamine loss. Although both the beta adrenergic and dopaminergic systems act together in mediating AMPH anorexia, the onset and the rate of completion of tolerance appear to be under the influence of hypothalamic dopaminergic system.