کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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2495047 | 1115593 | 2006 | 11 صفحه PDF | دانلود رایگان |
N-methyl-d-aspartate (NMDA) receptors play several essential roles in the physiology and pathophysiology of the brain. Their activation results in long-term changes in glutamatergic synaptic transmission in several brain areas, but excessive activation of these receptors induces neurotoxicity. Some of NMDA-mediated actions are critically dependent on functional interactions with the neuromodulator adenosine. In the present study, we have examined whether pharmacological activation of NMDA receptors induces long-term changes in synaptic strength in the striatum. We found that NMDA depressed the amplitude of the field excitatory postsynaptic potential/population spike (fEPSP/PS) recorded in corticostriatal mouse brain slices in a concentration-dependent manner. Inhibition of synaptic transmission was more pronounced at room temperature (22 °C) than at 32 °C and long lasting (>2 h) depression of the fEPSP/PS was observed only at room temperature. NMDA-induced depression of the fEPSP/PS was reduced or abolished in the presence of an A1 receptor antagonist and in A1 receptor knockout mice. In addition, exogenous application of adenosine depressed fEPSP/PS amplitude in wild-type mice, but not in A1 receptor knockout mice, in a concentration-dependent manner. Our results demonstrate that NMDA depresses synaptic transmission in a concentration- and temperature-dependent manner via release of adenosine and activation of adenosine A1 receptors.
Journal: Neuropharmacology - Volume 51, Issue 2, August 2006, Pages 272–282