Alteration of the neurochemical effects of fenfluramine by previous treatment with d-amphetamine.

It was found in an earlier study that a 15-day IP subacute d-amphetamine treatment rendered an apparent "tolerance" to the food intake suppressant effects of fenfluramine. The purpose of the present study was to determine if the neuronal substrate on which fenfluramine supposedly acts to produce a decrement in food consumption was altered by the previous treatment with d-amphetamine. The time course effects (0-90 min) of a single IP injection of 10 mg/kg fenfluramine on brain monoamines in saline-treated rats included a significant lowering of serotonin in all brain regions examined. Although the serotonin depleting actions of fenfluramine in the d-amphetamine-treated rats generally paralleled those seen in the saline group (i.e., as in the hypothalamus), no such effects were noted in regions where baseline values (see below) were already lowered by d-amphetamine treatment (i.e., pons-medulla, thalamus, and substantia nigra). Norepinephrine and dopamine depletions were observed in the pons-medulla and hypothalamic areas after fenfluramine administration in the saline-treated rats, but fenfluramine caused no decreases in hypothalamic dopamine or in pons-medulla and hypothalamic norepinephrine content in rats previously treated with d-amphetamine. Analysis of the baseline amine levels (i.e., values in the d-amphetamine and saline-treated rats before fenfluramine was given) indicated that the repeated d-amphetamine treatment generally lowered norepinephrine in most brain regions, serotonin in the pons-medulla, substantia nigra and thalamus, and dopamine in the striatum.(ABSTRACT TRUNCATED AT 250 WORDS)