ABSENCE OF 6-HYDROXYDOPAMINE IN THE RAT-BRAIN AFTER TREATMENT WITH STIMULANTS AND OTHER DOPAMINERGIC AGENTS - A MASS FRAGMENTOGRAPHIC STUDY

Formation of 6-hydroxydopamine (6-OHDA) from dopamine has been hypothe sized to mediate neuro-degeneration induced by some psychostimulants. Although the emergence of a 6-OHDA-like substance was reported in the striatum of methamphetamine-treated rats, this substance has not been identified by a direct approach. We used mass fragmentography to searc h for 6-OHDA in the rat frontal cortex and striatum after the administ ration of a number of drugs including 3,4-dihydroxyphenyl-L-alanine, m ethamphetamine, amphetamine, and cocaine, all of which increase synapt ic dopamine. No 6-OHDA was detected after the acute systemic administr ation of these agents. Intraventricular administration of 6-OHDA (10 m ug/rat) produced measurable concentrations of 6-OHDA that were higher in the striatum than in the frontal cortex. Intraventricular administr ation of 2,4,5-trihydroxyphenyl-D,L-alanine (6-OHDOPA; 10 mug/rat) pro duced similar concentrations of 6-OHDA in both regions. Pargyline, but not carbidopa (alpha-methyldopahydrazine), enhanced the effect of int raperitoneal 6-OHDOPA administration (80 mg/kg). We conclude that (1) 6-OHDOPA can cross the blood-brain barrier and is converted to 6-OHDA in the brain, (2) 6-OHDA is a substrate for monoamine oxidase(s) and t herefore a search for its purported deaminated metabolite is warranted , and (3) acute treatment with the above stimulants either does not le ad to the formation of 6-OHDA or produces concentrations below the det ection limit of the assay (< 34 pg/mg of protein).