Effects of amphetamine and amfonelic acid on the disposition of striatal newly synthesized dopamine.

A comparison of the in vivo biochemical actions of the psychotomimetic central stimulants, d-amphetamine (d-AMPH) and amfonelic acid (AFA), on the metabolism of rat striatal newly synthesized [3H]dopamine (DA) was made by pulse labeling with [3H]tyrosine. No evidence for the formation of the alcoholic DA metabolites [3H]3-methoxy-4-hydroxyphenylethanol (MOPET) or [3H]3,4-dihydroxyphenylethanol (DOPET) was found in control or drug-treated animals. Both [3H]3,4-dihydroxyphenylacetic acid (DOPAC) and [3H]homovanillic acid (HVA) concentrations were increased by AFA in the presence of haloperidol, while [3H]DA content was decreased. In contrast, d-AMPH, in the presence of haloperidol, decreased [3H]DOPAC and increased [3H]DA, even in monoamine oxidase-blocked rats. Thus monoamine oxidase inhibition did not appear to be a major factor in the action of amphetamine to increase [3H]DA, but cannot be excluded as a contributing factor to the lowering of [3H]DOPAC. Similar actions of d-AMPH were seen on preformed DA. Amphetamine may release newly synthesized DA in such a way that some of the released DA enters the neuronal storage system.