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 hypothesized 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 search for 6‐OHDA in the rat frontal cortex and striatum after the administration of a number of drugs including 3,4‐dihy‐droxyphenyl‐L‐alanine, methamphetamine, amphetamine, and cocaine, all of which increase synaptic dopamine. No 6‐OHDA was detected after the acute systemic administration of these agents. Intraventricular administration of 6‐OHDA (10 μg/rat.) produced measurable concentrations of 6‐OHDA that were higher in the striatum than in the frontal cortex. Intraventricular administration of 2,4,5‐trihydroxy‐phenyl‐D,L‐alanine (6‐OHDOPA; 10 μg/rat) produced similar concentrations of 6‐OHDA in both regions. Pargyline, but not carbidopa (α‐methyldopahydrazine), enhanced the effect of intraperitoneal 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 therefore a search for its purported deaminated metabolite is warranted, and (3) acute treatment with the above stimulants either does not lead to the formation of 6‐OHDA or produces concentrations below the detection limit of the assay (