THE STRIATONIGRAL DYNORPHIN PATHWAY OF THE RAT STUDIED WITH IN-VIVO MICRODIALYSIS .1. EFFECTS OF K-DEPOLARIZATION, LESIONS AND PEPTIDASE INHIBITION()

Extracellular levels of dynorphin B were analysed with in vivo microdi alysis in the neostriatum and substantia nigra of halothane-anaestheti zed rats. Dopamine and its metabolites, 3,4-dihydroxyphenylacetic acid and homovanillic acid, as well as GABA were simultaneously monitored. Chromatographic analysis revealed that the dynorphin B-like immunorea ctivity measured in perfusates collected under basal and K+-depolarizi ng conditions co-eluted with synthetic dynorphin B. Dynorphin B, GABA and dopamine levels were Ca2+-dependently increased by K+-depolarizati on, while 3,4-dihydroxyphenylacetic acid and homovanillic acid levels were decreased. Dopamine and its metabolites, but not dynorphin B or G ABA levels, were significantly decreased after a unilateral 6-hydroxyd opamine injection into the left medial forebrain bundle. In contrast, following a unilateral injection of ibotenic acid into the striatum, d ynorphin B and GABA levels were decreased by >50% in striatum and subs tantia nigra on the lesioned side, whereas no significant changes were observed in basal dopamine levels. The inclusion of the peptidase inh ibitor captopril (50-500 mu M) into the nigral perfusion medium produc ed a concentration-dependent increase in nigral extracellular levels o f dynorphin B. In the striatum, a delayed increase in dynorphin B and GABA levels could be observed following the nigral captopril administr ation, but this effect was not concentration-dependent. Thus, we demon strate 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 Ca2+-dependent manner by K+-depolarization, and (ii ) decreased by a selective lesion of the striatum, known to contain ce ll bodies of dynorphin neurons in the striatonigral pathway. Furthermo re, (iii) the increase in nigral dynorphin B levels by peptidase inhib ition suggests the presence of clearance mechanisms for the released d ynorphin peptides.