A KINETIC-ANALYSIS OF THE EFFECTS OF BETA-PHENYLETHYLAMINE ON THE CONCENTRATIONS OF DOPAMINE AND ITS METABOLITES IN THE RAT STRIATUM

The purpose of this investigation was to determine whether the increas e in the dopamine (DA) concentration in the rat striatum after a rapid iv injection of beta-phenylethylamine (PEA) can be quantitatively exp lained by the alteration of the striatum PEA concentration using a con structed DA metabolism model and to examine whether the time courses o f the striatum DA metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) a nd homovanillic acid (HVA) concentration can be described by this DA m etabolism model. The time courses of PEA concentration in plasma and t he striatum were determined by gas chromatography-mass spectrometry. T he plasma PEA concentration was described by a two-compartment model w ith nonlinear elimination kinetics. The striatum PEA concentration was about 10 times higher than the plasma PEA concentration. The time cou rse of the striatum PEA concentration was described by a diffusion-lim ited model including a Michaelis-Menten type transport system from pla sma to the striatum and nonlinear elimination from the striatum. The D A concentration in the striatum increased immediately after PEA inject ion. In contrast, the DOPAC concentration in the striatum decreased im mediately. HVA concentration in the striatum increased gradually. Assu ming that the enhancement of DA concentration in the striatum after PE A injection is caused by the competitive inhibition of PEA on the reup take of DA into DA neuronal terminals (and the metabolism from DA to D OPAC is then competitively inhibited by PEA in the DA neuronal termina ls), the relationship between the enhancement of DA concentration and PEA concentration in the striatum was analyzed using a constructed DA metabolism model. The enhancement of the DA concentration in the stria tum was described quantitatively by this model. Thus, it was clarified that a quantitative relationship between PEA concentration and the en hancement of DA concentration in the striatum is present after PEA inj ection. However, the time courses of the striatum DOPAC (lower dose) a nd HVA (time delay) concentrations could not be described by this mode l. These results indicated that other factors might be necessary to ex plain the time courses of the DOPAC and HVA concentrations in the stri atum after PEA injection, such as the separate evaluation of the effec t of PEA on the reuptake of DA into DA neuronal terminals and on the m onoamine oxidase-B (MAO-B) activity in the DA neuronal terminals, and the metabolic pathway from DOPAC to HVA.