Locus ceruleus lesion by local 6-hydroxydopamine infusion causes marked and specific destruction of noradrenergic neurons, long-term depletion of norepinephrine and the enzymes that synthesize it, and enhanced dopaminergic mechanisms in the ipsilateral cerebral cortex.

The local stereotaxic microinfusion of 5 micrograms of 6-hydroxydopamine in the region of the nucleus locus ceruleus causes severe loss of noradrenergic neurons with little evidence of nonspecific tissue reaction or destruction that could be detected by conventional light microscopic methods. Such lesion is accompanied by a marked and long-term depletion of norepinephrine and comparable loss of activity of its synthesizing enzymes, dopamine beta-hydroxylase and tyrosine hydroxylase, in the ipsilateral cerebral cortex. Locus ceruleus lesion was also found to increase tissue levels of dopamine and its metabolites, 3,4-dihydroxyphenylacetic acid and homovanillic acid, in the ipsilateral cortex. These results add further evidence to support the hypothesis that enhanced dopaminergic mechanisms may play a central role in compensating for chronic cortical noradrenergic denervation.