Neurotensin regulates cortical glutamate transmission by modulating N-methyl-D-aspartate receptor functional activity: An in vivo microdialysis study
✍ Scribed by Luca Ferraro; Sarah Beggiato; Maria Cristina Tomasini; Kjell Fuxe; Sergio Tanganelli; Tiziana Antonelli
- Publisher
- John Wiley and Sons
- Year
- 2011
- Tongue
- English
- Weight
- 201 KB
- Volume
- 89
- Category
- Article
- ISSN
- 0360-4012
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✦ Synopsis
The aim of the present in vivo microdialysis study was to investigate whether the tridecapeptide neurotensin (NT) influences the N-methyl-D-aspartate (NMDA) receptormediated increase of cortical glutamate transmission in freely moving rats. Intracortical perfusion with NT influenced local extracellular glutamate levels in a bell-shaped, concentration-dependent manner. One hundred and three hundred nanomolar NT concentrations increased glutamate levels (151% 6 7% and 124% 6 3% of basal values, respectively). Higher (1,000 nM) and lower (10 nM) NT concentrations did not alter extracellular glutamate levels. The NT receptor antagonist SR48692 (100 nM) prevented the NT (100 nM)-induced increase in glutamate levels. NMDA (100 and 500 lM) perfusion induced a concentration-dependent increase in extracellular glutamate levels, the lower 10 lM NMDA concentration being ineffective. When NT (10 nM, a concentration by itself ineffective) was added in combination with NMDA (100 lM) to the perfusion medium, a significant greater increase in extracellular glutamate levels (169% 6 7%) was observed with respect to the increase induced by NMDA (100 lM) alone (139% 6 4%). SR48692 (100 nM) counteracted the increase in glutamate levels induced by the treatment with NT (10 nM) plus NMDA (100 lM). The enhancement of cortical glutamate levels induced by NMDA (100 and 500 lM) was partially antagonized by the presence of SR48692, at a concentration (100 nM) that by itself was ineffective in modulating glutamate release. These findings indicate that NT plays a relevant role in the regulation of cortical glutamatergic transmission, especially by modulating the functional activity of cortical NMDA receptors. A possible role in glutamate-mediated neurotoxicity is suggested. V