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
posted on 2015-06-18, 08:32authored byLuca Ferraro, Tiziana Antonelli, William T. O'Connor, Kjell Fuxe, Philippe Soubrié, Sergio Tanganelli
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 NTinduced
increase in pallidal glutamate release was also
investigated.
Intrastriatal NT (100 and 300 nM) increased striatal glutamate
and GABA (100 nM, 155 6 9 and 141 6 6%, respectively;
300 nM, 179 6 8 and 166 6 11%, respectively) release,
as well as pallidal glutamate and GABA (100 nM, 144 6 8 and
130 6 5%; 300 nM, 169 6 9 and 157 6 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
(2)-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 (2)-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
History
Publication
The Journal of Neuroscience;18, (17), pp. 6977-6989