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. Furthermore, the decreased nigral release of SP and NKA ipsilateral to the lesion is suggested to be caused by an increased GABA inhibition in striatum of SP- and NKA-containing striato-nigral neurons.