Neurochemical characterization of the actions of 5-amino-2,4- dihydroxy-alpha-methylphenylethylamine (5-ADMP): a selective neurotoxin to central noradrenergic neurons.
The concentrations of amine neurotransmitters [dopamine (DA), norepinephrine (NE) and 5-hydroxytryptamine] and some of their deaminated metabolites [dihydroxyphenylacetic acid and 5-hydroxyindoleacetic acid] were determined in selected regions of the rat brain, including several hypothalamic nuclei, at various times after the i.c.v. injection of various doses of 5-amino-2,4-dihydroxy-alpha-methylphenylethylamine (5-ADMP). Seven days after a single i.c.v. injection of 100 micrograms of 5-ADMP the concentration of NE in all brain regions examined was reduced markedly, as was the concentration of DA in the median eminence. The concentrations of DA and dihydroxyphenylacetic acid in regions other than the median eminence, and the concentrations of 5-hydroxytryptamine and 5-hydroxyindoleacetic acid in all regions analyzed were unaltered. Multiple injections of 5-ADMP (100 micrograms i.c.v. every 48 hr X 3) did not increase the NE depletion, but caused slight decreases in DA and 5-hydroxytryptamine in some regions. The NE concentrations in hypothalamic nuclei were reduced significantly 4 hr after 100 micrograms i.c.v. administration of 5-ADMP and this depletion was maintained for at least 28 days. The 5-ADMP-induced decline of NE in all brain region, but not the decline of DA in the median eminence, was prevented partially by pretreatment with desipramine. These results indicate that 5-ADMP is a relatively specific neurotoxin for NE neurons, being particularly effective in destroying NE nerve terminals in the hypothalamus.