Different effects of amphetamine and amfonelic acid on peripheral and central catecholamine metabolism

Abstract

The effects of amphetamine (AMPH) and a non-amphetamine stimulant, amfonelic acid (AFA), on catecholamine metabolism in peripheral sympathetic ganglia (superior cervical and celiac) and several brain regions (hypothalamus, caudate, olfactory tubercle and nucleus accumbens) were examined. The effects of the drugs on gross behavior measures (hyperactivity with some stereotypy) were similar. In the sympathetic ganglion (both intact and decentralized superior cervical ganglia included) AMPH significantly elevated dopamine, with a non-significant reduction in norepinephrine. Three, 4-dihydroxyphenylacetic acid (DOPAC) was significantly decreased, in the celiac ganglion, but not in the superior cervial ganglion. Amfonelic acid had no effect on catecholamines in the ganglia. The effect of AMPH on superior cervical ganglion SIF-cells dopamine concentration is therefore local and independent on the preganglionic nerve. In all the brain regions analyzed AMPH significantly increased norepinephrine and dopamine concentrations, with only minor effects on their metabolites (caudate and accumbens DOPAC decreased). Amfonelic acid, on the other hand primarily elevated dopamine metabolism. It decreased norepinephrine in the olfactory tubercle and accumbens, and increased 3-methoxy-4-hydroxyphenylglycol concentration in the hypothalamus. This latter suggests an influence of AFA on central noradrenergic neurons. At the doses used neither drug significantly altered caudate monoamine oxidase activity. Since desmethylimipramine produced different effects on catecholamine metabolism than AFA, it is unlikely that AFA works by blocking norepinephrine reuptake. Desmethylimipramine in contrast to AFA, reduced the metabolism of both norepinephrine and dopamine in the caudate and hypothalamus. Our results are consistent with the concept that AMPH acts to release amines and shuts down catecholaminergic neuronal firing, while AFA facilitates impulse-induced release and stimulates central catecholamine turnover. γ-Butyrolactone, which blocks dopaminergic impulse flow, antagonized the hyperactive effects of AFA but not its biochemical actions,suggesting that other transmitter systems are involved or that γ-butyrolactone produced a non-specific, generalized depression of activity. The stimulant effects of AMPH, AFA and desmethylimipramine do not appear to be directly related to their influence on central catecholamines.