Abstract：
:Stereotaxically placed intracerebral microinjections of 6-hydroxydopamine (6-OHDA) were used to produce selective and extensive lesions of either the dopaminergic nigro-neostriatal bundle or the dorsal and ventral noradrenergic projections in the rat. The extensive damage of the noradrenergic pathways which is typically obtained after intranigral 6-OHDA injections was completely prevented by pretreatment with desipramine. Extensive depletions (85-95%) of norepinephrine (NE) in the hypothalamus, cerebral cortices and hippocampi failed to influence either spontaneous or D-amphetamine-induced locomotor activity. Neither the time course of the amphetamine response as measured by photocell cages nor the qualitative nature of the response as determined by direct observation was significantly altered by these lesions. In contrast, selective depletion (92%) of neostriatal dopamine (DA) after intranigral 6-OHDA injections severly reduced but did not abolish amphetamine-induced hyperkinesia. At the highest dose studied (2.0 mg/kg) these animals showed an initial increase in activity but, unlike controls, failed to maintain this level. This response was probably mediated by the small remaining stores of DA in the neostriatum. Pimozide (0.5 mg/kg) also severely attenuated but did not abolish amphetamine-induced locomotor activity. These data are consistent with the view that ascending DA projections are a critical substrate for amphetamine-induced hyperkinesia. They furthermore suggest that ascending NE systems do not play a role in this response.
journal_name
Brain Resjournal_title
Brain researchauthors
Roberts DC,Zis AP,Fibiger HCdoi
10.1016/0006-8993(75)90182-1subject
Has Abstractpub_date
1975-08-15 00:00:00pages
441-54issue
3eissn
0006-8993issn
1872-6240pii
0006-8993(75)90182-1journal_volume
93pub_type
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