The striatonigral dynorphin pathway of the rat studied with in vivo microdialysis--I. Effects of K(+)-depolarization, lesions and peptidase inhibition.
Extracellular levels of dynorphin B were analysed with in vivo microdialysis in the neostriatum and substantia nigra of halothane-anaesthetized rats. Dopamine and its metabolites, 3,4-dihydroxyphenyl-acetic acid and homovanillic acid, as well as GABA were simultaneously monitored. Chromatographic analysis revealed that the dynorphin B-like immunoreactivity measured in perfusates collected under basal and K(+)-depolarizing conditions co-eluted with synthetic dynorphin B. Dynorphin B, GABA and dopamine levels were Ca(2+)-dependently increased by K(+)-depolarization, while 3,4-dihydroxyphenylacetic acid and homovanillic acid levels were decreased. Dopamine and its metabolites, but not dynorphin B or GABA levels, were significantly decreased after a unilateral 6-hydroxydopamine injection into the left medial forebrain bundle. In contrast, following a unilateral injection of ibotenic acid into the striatum, dynorphin B and GABA levels were decreased by > 50% in striatum and substantia nigra on the lesioned side, whereas no significant changes were observed in basal dopamine levels. The inclusion of the peptidase inhibitor captopril (50-500 microM) into the nigral perfusion medium produced a concentration-dependent increase in nigral extracellular levels of dynorphin B. In the striatum, a delayed increase in dynorphin B and GABA levels could be observed following the nigral captopril administration, but this effect was not concentration-dependent. Thus, we demonstrate that extracellular levels of dynorphin B, dopamine and GABA can simultaneously be monitored with in vivo microdialysis. Extracellular dynorphin B appears to originate from neurons, since the levels were (i) increased in a Ca(2+)-dependent manner by K(+)-depolarization, and (ii) decreased by a selective lesion of the striatum, known to contain cell bodies of dynorphin neurons in the striatonigral pathway. Furthermore, (iii) the increase in nigral dynorphin B levels by peptidase inhibition suggests the presence of clearance mechanisms for the released dynorphin peptides.
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Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden.
Nylander
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Herrera-Marschitz
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O'Connor
W T
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Goiny
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Terenius
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D000818:Animals; D002216:Captopril / Q000494:pharmacology; D002845:Chromatography; D003342:Corpus Striatum / Q000502:physiology*; D004298:Dopamine / Q000378:metabolism; D004399:Dynorphins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D004594:Electrophysiology; D004723:Endorphins / Q000737:chemistry / Q000378:metabolism; D005110:Extracellular Space / Q000378:metabolism; D008297:Male; D017551:Microdialysis; D009434:Neural Pathways / Q000502:physiology; D011188:Potassium / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013378:Substantia Nigra / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D004723:Endorphins; D005680:gamma-Aminobutyric Acid; D004399:Dynorphins; C036200:rimorphin; D002216:Captopril; D011188:Potassium; D004298:Dopamine