 |
 Previous Article | Next Article 
The Journal of Neuroscience, September 1, 1998, 18(17):6977-6989
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
Luca
Ferraro1,
Tiziana
Antonelli1,
William T.
O'Connor2,
Kjell
Fuxe3,
Philippe
Soubrié4, and
Sergio
Tanganelli1
1 Department of Clinical and Experimental Medicine,
Pharmacology Section, University of Ferrara, 44100 Ferrara, Italy,
2 Department of Human Anatomy and Physiology, University
College of Dublin, Dublin, Ireland, 3 Department of
Neuroscience, Karolinska Institute, Stockholm, Sweden, and
4 Sanofi Recherche, 34184 Cedex 04, Montpellier,
France
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.
Key words:
basal ganglia; striatum; globus pallidus; neurotensin; SR48692; microdialysis; awake rat
Copyright © 1998 Society for Neuroscience 0270-6474/98/18176977-13$05.00/0
This article has been cited by other articles:
|
|
|
|
 
T. Antonelli, M. C. Tomasini, J. Fournier, R. Mazza, S. Tanganelli, S. Pirondi, K. Fuxe, and F. Luca
Neurotensin Receptor Involvement in the Rise of Extracellular Glutamate Levels and Apoptotic Nerve Cell Death in Primary Cortical Cultures after Oxygen and Glucose Deprivation
Cereb Cortex,
August 1, 2008;
18(8):
1748 - 1757.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Li, J. D. Geiger, and S. Lei
Neurotensin Enhances GABAergic Activity in Rat Hippocampus CA1 Region by Modulating L-Type Calcium Channels
J Neurophysiol,
May 1, 2008;
99(5):
2134 - 2143.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. M. Torregrossa and P. W. Kalivas
Neurotensin in the Ventral Pallidum Increases Extracellular {gamma}-Aminobutyric Acid and Differentially Affects Cue- and Cocaine-Primed Reinstatement
J. Pharmacol. Exp. Ther.,
May 1, 2008;
325(2):
556 - 566.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. A. Petrie, D. Schmidt, M. Bubser, J. Fadel, R. E. Carraway, and A. Y. Deutch
Neurotensin Activates GABAergic Interneurons in the Prefrontal Cortex
J. Neurosci.,
February 16, 2005;
25(7):
1629 - 1636.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. F. Finnegan, S.-R. Chen, and H.-L. Pan
Effect of the {micro} Opioid on Excitatory and Inhibitory Synaptic Inputs to Periaqueductal Gray-Projecting Neurons in the Amygdala
J. Pharmacol. Exp. Ther.,
February 1, 2005;
312(2):
441 - 448.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Antonelli, L. Ferraro, K. Fuxe, S. Finetti, J. Fournier, S. Tanganelli, M. De Mattei, and M. C. Tomasini
Neurotensin Enhances Endogenous Extracellular Glutamate Levels in Primary Cultures of Rat Cortical Neurons: Involvement of Neurotensin Receptor in NMDA Induced Excitotoxicity
Cereb Cortex,
April 1, 2004;
14(4):
466 - 473.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. R. Dobner, J. Fadel, N. Deitemeyer, R. E. Carraway, and A. Y. Deutch
Neurotensin-deficient mice show altered responses to antipsychotic drugs
PNAS,
June 20, 2001;
(2001)
141042198.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. R. Dobner, J. Fadel, N. Deitemeyer, R. E. Carraway, and A. Y. Deutch
Neurotensin-deficient mice show altered responses to antipsychotic drugs
PNAS,
July 3, 2001;
98(14):
8048 - 8053.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
