Tissue levels and in vivo release of tachykinins and GABA in striatum and substantia nigra of rat brain after unilateral striatal dopamine denervation

Abstract

Brain tissue levels and in vivo release of substance P (SP) and neurokinin A (NKA) and GABA were measured bilaterally in striatum and substantia nigra of the rat, after a unilateral 6-hydroxydopamine lesion of the nigro-striatal dopamine pathway. Sham injected animals served as controls. The dopamine denervation decreased the tissue levels of SP in striatum (-38%) ipsilateral to the lesion and in substantia nigra both ipsi- (-54%) and contralateral (-38%) to the lesion. NKA was not significantly changed in the striatum, but decreased (like SP) in the substantia nigra both ipsi- (-50%) and contralateral (-40%) to the lesion. GABA tissue levels increased in the denervated striatum (+20%) and remained unchanged in substantia nigra at both sides. The extracellular levels of SP, NKA and GABA were measured with microdialysis in vivo at basal conditions and during stimulation with potassium administered locally via the microdialysis probe. The stimulated release of SP and NKA in the substantia nigra ipsilateral to the lesion was compared to in sham operated animals reduced with 39% and 64%, respectively, while no change in SP or NKA release was detected in the striatum. The basal release of GABA in the striatum was increased with 296% and with 76% during stimulation in the dopamine denervated striatum, while no change in GABA basal or stimulated release was detected in the substantia nigra. We suggest that the increased GABA release in the dopamine denervated striatum may be due to a decreased dopamine mediated inhibition of local GABA neurons.(ABSTRACT TRUNCATED AT 250 WORDS)

Recurrent Collateral Connections of Striatal Medium Spiny Neurons Are Disrupted in Models of Parkinson's Disease

“…Preliminary experiments suggest that GABA release at these synapses is not depressed, implicating intrastriatal regulatory mechanisms. Interestingly, microdialysis studies suggested that depolarization-induced release of GABA in rats striatum increases after DA depletion (Lindefors et al, 1989;Campbell et al, 1993;Abarca and Bustos, 1999). In light of our results, the most parsimonious interpretation of these findings is that they are detecting primarily GABA released from interneurons.…”

Neurokinin receptors differentially mediate endogenous acetylcholine release evoked by tachykinins in the neostriatum

“…The first pattern is consistent with a downregulation, leading to a decrease in striatal SP levels (Voom et al, 1987), SP mRNA (Young et al, 1986;Sivam et al, 1987) and dynorphin levels (Jiang et al, 1990). This downregulation was followed neither by the release of SP and NKA in the neostriatum (Lindefors et al, 1989) nor by altering the effects of SP and NKA on ACh release in the 6-OHDA-lesioned striatum (present results). Instead, the dopaminergic denervation decreased SP and NKA release in the substantia nigra (Lindefors et al, 1989).…”

“…This downregulation was followed neither by the release of SP and NKA in the neostriatum (Lindefors et al, 1989) nor by altering the effects of SP and NKA on ACh release in the 6-OHDA-lesioned striatum (present results). Instead, the dopaminergic denervation decreased SP and NKA release in the substantia nigra (Lindefors et al, 1989). Thus, it is likely that the downregulation of SP levels (Voom et al, 1987) and mRNA (Young et al, 1986;Sivam et al, 1987) in the neostriatum reflected the dopaminergic regulation of SP/NKA striatonigral neurons together with a masked or absent dopaminergic regulation of SP/NKA interneurons.…”

“…The second pattern of regulation of striatal neuronal activity is consistent with an upregulation of other neuronal systems, which leads to an increase in GABA levels (Lindefors et al, 1989) glutamic acid decarboxylase levels (Vernier et al, 1988) enkephalin mRNA (Young et al, 1986;Sivam et al, 1987;Vernier et al, 1988), enkephalin levels (Voom et al, 1987;Jiang et al, 1990) and NKB mRNA (Burgunder and Young, 1989). These changes have also been reported to be followed by an increase in the release of some of these neurotransmitters such as GABA (Lindefors et al, 1989).…”

“…The activation of NK receptors induces excitatory effects in several neural systems and releases many neuroactive substances (Maggio, 1988;Kangrga and Randic, 1990;Reid et al, 1990). Both in vitro (Lindefors et al, 1985) and in vivo (Lindefors et al, 1989) experiments have shown that TKs are released in a Ca*+ -dependent fashion in the neostriatum.…”