Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8479402 | Neurochemistry International | 2008 | 5 Pages |
Abstract
Single neuron firing rate was recorded from dorsal raphe nucleus of anesthetized rats. The firing rate of raphe neurons varied from 4 to 8 discharge per second before drug administration and this neuronal activity was decreased by L-701,324 (2Â mg/kg i.v. injection), a competitive antagonist of glycineB binding site of N-methyl-d-aspartate (NMDA) receptors. The glycine transporter type-1 (GlyT1) antagonists Org-24461 (10Â mg/kg i.v.) and NFPS (3Â mg/kg i.v.) reversed the inhibitory effect of L-701,324 on single neuron activity recorded from dorsal raphe nucleus of the rat. Org-24461 and NFPS both tended to increase the raphe neuronal firing rate also when given alone but their effect was not significant. This finding serves further evidence that glutamate released from axon terminals of the cortico-striatal projection neurons stimulates serotonergic neurons in the raphe nuclei and this effect is mediated at least in part by postsynaptic NMDA receptors. Thus, GlyT1 inhibitors are able to reverse the hypofunctional state of NMDA receptors, suggesting that these drugs may have beneficial therapeutic effects in neurological and psychiatric disorders characterized with impaired NMDA receptor-mediated transmission.
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Authors
Andras Papp, Zsolt Juranyi, Laszlo Nagymajtenyi, Peter Matyus, Laszlo G. Jr.,