Neuronal degeneration in rat brain induced by 6-hydroxydopamine; a histological and biochemical study

J. C. Hedreen, J. P. Chalmers

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139 Citations (Scopus)


6-OHDA injected into the cerebrospinal fluid of the rat causes a fall in brain NE and DA levels, accompanied by degeneration of neuronal perikarya in SN and in adjacent VTA and lateral tegmentum, and terminal degeneration in CP, NAcc and OT demonstrable by the Nauta-Gygax and Fink-Heimer silver methods. NE levels fell to 5% of normal 14 days after a high dose (200 μg + 400 μg) of 6-OHDA, and DA levels to 17%. Even the more moderate declines in catecholamine levels following 200 μg 6-OHDA were accompanied by florid argyrophilic neuronal degeneration. The location of the terminal degeneration is very similar to that of DA-containing terminals identified by use of the histofluorescence method for monoamines. The location of degenerating cell bodies in SN closely corresponds to that of perikarya found by the histofluorescence method to contain dopamine, but the distribution in tegmentum and VTA is more restricted. Occasional cell bodies were seen to degenerate in the locus coeruleus and a few other areas after high doses of 6-OHDA. A group of degenerating axons of unusual appearance was found, probably afferent to NAcc and OT. No degeneration was seen in areas in which NE-containing terminals have been reported, despite reports of electron microscopic evidence of bouton degeneration in such areas elicited by 6-OHDA, and despite the severe decline in brain NE content in the higher-dose group. Nor was any change seen in the infundibular nucleus and median eminence, regions in which DA-containing neurons have been reported. Electrolytic SN lesions cause dense terminal degeneration in CP indistinguishable from that caused by 6-OHDA injection into the CSF. Only sparse terminal degeneration appeared in CP if electrolytic SN lesions were placed in rats that had received 6-OHDA several weeks prior to surgery. Large SN lesions in such pretreated animals induce a tendency to turn in circles away from the lesioned side.

Original languageEnglish
Pages (from-to)1-36
Number of pages36
JournalBrain Research
Issue number1
Publication statusPublished - 27 Nov 1972
Externally publishedYes


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