title: Influence of nigrostriatal dopaminergic tone on the biosynthesis of dynorphin and enkephalin in rat striatum.
abstract: The purpose of this study was to obtain direct evidence that the nigrostriatal dopamine (DA) pathway modulates the metabolism of striatal dynorphin and [Met5]-enkephalin. This was achieved by repeated injections of apomorphine (APO) or D-amphetamine (AMP) in unilateral nigral 6-hydroxydopamine (6-OHDA)-lesioned rats. Three weeks after a 6-OHDA lesion, dynorphin A(1-8)-like immunoreactivity (DN-LI) and the level of mRNA encoding prodynorphin in the striatum on the lesioned side were decreased compared with the contralateral control side. Activation of DA receptors by 7 daily injections of APO (5 mg/kg, Bid, s.c.), however, caused a large increase (3- to 4-fold of saline control) in striatal levels of DN-LI and prodynorphin mRNA on the 6-OHDA lesioned side, which is far greater than the increase on the contralateral side (2-fold of saline control). Presumably, the potentiated effect of APO in 6-OHDA lesioned rats is due to hypersensitivity of DA receptors resulting from DA denervation. Seven daily injections of AMP (5 mg/kg, Bid, s.c.), a DA-releasing agent, increased striatal DN-LI (187% of saline control) on the non-lesioned side, but not on the 6-OHDA-lesioned side. Taken together, the data indicate that the nigrostriatal pathway exerts a tonic excitatory influence over the biosynthesis of dynorphin and that this influence is not maximal since an additional increase in dopaminergic tone further increases the expression of dynorphin. In contrast, [Met5]-enkephalin-like immunoreactivity (ME-LI) in the striatum was increased by a 6-OHDA-lesion (145% of contralateral control), which was blocked by repeated administration of APO but not AMP.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Laboratory of Molecular and Integrative Neuroscience, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709.
authors.forename: S J
authors.initials: SJ
authors.lastname: Li
authors.forename: H K
authors.initials: HK
authors.lastname: Jiang
authors.forename: M S
authors.initials: MS
authors.lastname: Stachowiak
authors.forename: P M
authors.initials: PM
authors.lastname: Hudson
authors.forename: V
authors.initials: V
authors.lastname: Owyang
authors.forename: K
authors.initials: K
authors.lastname: Nanry
authors.forename: H A
authors.initials: HA
authors.lastname: Tilson
authors.forename: J S
authors.initials: JS
authors.lastname: Hong
mesh_terms: D000818:Animals; D001058:Apomorphine / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D003913:Dextroamphetamine / Q000494:pharmacology*; D004298:Dopamine / Q000502:physiology*; D004399:Dynorphins / Q000096:biosynthesis* / Q000235:genetics; D004745:Enkephalins / Q000096:biosynthesis*; D006892:Hydroxydopamines / Q000494:pharmacology; D008297:Male; D016627:Oxidopamine; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D051381:Rats; D011916:Rats, Inbred F344; D012016:Reference Values; D013378:Substantia Nigra / Q000187:drug effects / Q000502:physiology*
chemical_list: D004745:Enkephalins; D006892:Hydroxydopamines; D012333:RNA, Messenger; D004399:Dynorphins; D016627:Oxidopamine; D001058:Apomorphine; D003913:Dextroamphetamine; D004298:Dopamine