Release of endogenous catecholamines from isolated rat brain tissue by fenfluramine and N-ethylamphetamine—effects of pargyline

Abstract

The influence of the monoamine oxidase inhibitor, pargyline. upon the release of endogenous norepinephrine from chopped rat cerebral cortex and endogenous dopamine from chopped rat corpus striatum by fenfluramine and N-ethylamphetamine was examined. Endogenous norepinephrine and dopamine were measured using an enzymatic-isotopic assay. Both fenfluramine and N-ethylamphetamine released significant amounts of each catecholamine. Fenfluramine-induced catecholamine release was associated with the decrease in the total content (i.e. catecholamine in media + catecholamine in tissue) of both cortical norepinephrine and striatal dopamine; N-elhylamphetamine decreased only total striatal dopamine content. In brain tissue obtained from rats pretreated with pargyline HCl (100 mg/kg, 12 hr prior to sacrifice), total cortical norepinephrine content was approximately twice that in the absence of pargyline: striatal dopamine was unchanged. Pargyline pretreatment also resulted in a marked potentiation of the amounts of both catecholamines released by each drug. and in an antagonism of the above drug-induced reductions in catecholamine content. Additionally, after pargyline pretreatment. N-ethylamphetamine reduced total cortical norepinephrine content. When pargyline (2.56 × 10 −1 M) was added to the media containing chopped cortical tissue from unpretreated animals, control content was slightly increased. Only fenfluramine-induced norepinephrine release was potentiated and the degree of potentiation was less than that observed after pargyline pretreatment. As with pargyline in vivo, pargyline in vitro also resulted in an antagonism of the fenfluramine-induced decrease in total norepinephrine and was associated with an N-ethylamphetamine-induced decrease in norepinephrine content. Since the locomotor stimulant effects of both fenfluramine and N-ethylamphetamine are potentiated after pargyline. the data are consistent with the importance of catecholamines to these effects. The data also suggest that pargyline potentiates the behavioral effects of fenfluramine and N-ethylamphetamine in part by increasing the pool of norepinephrine available for release by these drugs and in part by inhibiting the deamination of the released norepinephrine and dopamine by monoamine oxidase. Decreases in total norepinephrine produced by N-ethylamphetamine may reflect alterations in the formation of O-methylated amines.