RT Journal Article
SR Electronic
T1 The Striatal Neurotensin Receptor Modulates Striatal and Pallidal Glutamate and GABA Release: Functional Evidence for a Pallidal Glutamate–GABA Interaction via the Pallidal–Subthalamic Nucleus Loop
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 6977
OP 6989
DO 10.1523/JNEUROSCI.18-17-06977.1998
VO 18
IS 17
A1 Luca Ferraro
A1 Tiziana Antonelli
A1 William T. O’Connor
A1 Kjell Fuxe
A1 Philippe Soubrié
A1 Sergio Tanganelli
YR 1998
UL http://www.jneurosci.org/content/18/17/6977.abstract
AB In the present study, we used dual-probe microdialysis to investigate the effects of intrastriatal perfusion with neurotensin (NT) on striatal and pallidal glutamate and GABA release. The role of the pallidal GABAA receptor in the intrastriatal NT-induced increase in pallidal glutamate release was also investigated.Intrastriatal NT (100 and 300 nm) increased striatal glutamate and GABA (100 nm, 155 ± 9 and 141 ± 6%, respectively; 300 nm, 179 ± 8 and 166 ± 11%, respectively) release, as well as pallidal glutamate and GABA (100 nm, 144 ± 8 and 130 ± 5%; 300 nm, 169 ± 9 and 157 ± 8%, respectively) release. These effects were dose-dependently antagonized by the NT receptor antagonist 2-[(1-(7-chloro-4-quinolinyl)-5-(2,6-dimethoxy-phenyl)pyrazol-3-yl)carboxylamino]tricyclo)3.3.1.1.3.7)-decan-2-carboxylic acid (SR48692).Intrasubthalamic injection of the GABAA receptor antagonist (−)-bicuculline (10 pmol/100 nl, 30 sec) rapidly increased pallidal glutamate release, whereas the intrastriatal NT-induced increase in pallidal glutamate release was counteracted by intrapallidal perfusion with (−)-bicuculline, suggesting that an increase in striopallidal GABA-mediated inhibition of the GABAergic pallidal–subthalamic pathway results in an increased glutamatergic drive in the subthalamic–pallidal pathway.These results demonstrate a tonic pallidal GABA-mediated inhibition of excitatory subthalamic–pallidal neurons and strengthen the evidence for a functional role of NT in the regulation of glutamate and GABA transmission in the basal ganglia. The ability of intrastriatal SR48692 to counteract the NT-induced increase in both striatal and pallidal glutamate and GABA release suggests that blockade of the striatal NT receptor may represent a possible new therapeutic strategy in the treatment of those hypokinetic disorders implicated in disorders of the indirect pathway mediating motor inhibition.