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.
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.[1]References
- 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. Ferraro, L., Antonelli, T., O'Connor, W.T., Fuxe, K., Soubrié, P., Tanganelli, S. J. Neurosci. (1998) [Pubmed]
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