ATTENUATION OF NOCICEPTIVE RESPONSES BY ACEA-1021, A COMPETITIVE NMDARECEPTOR GLYCINE SITE ANTAGONIST, IN THE MICE

Authors
Citation
K. Lutfy et E. Weber, ATTENUATION OF NOCICEPTIVE RESPONSES BY ACEA-1021, A COMPETITIVE NMDARECEPTOR GLYCINE SITE ANTAGONIST, IN THE MICE, Brain research, 743(1-2), 1996, pp. 17-23
Citations number
32
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Neurosciences
Journal title
Brain research → ACNP
ISSN journal
0006-8993
Volume
743
Issue
1-2
Year of publication
1996
Pages
17 - 23
Database
ISI
SICI code
0006-8993(1996)743:1-2<17:AONRBA>2.0.ZU;2-G
Abstract
Intrathecal administration of N-methyl-D-aspartate (NMDA) and non-NMDA receptor antagonists has been shown to produce antinociception in var ious animal models of pain. In the present study we examined the effec t of itro-6,7-dichloro-1,4-dihydro-2,3-quinoxalinedione (ACEA-1021), a competitive NMDA receptor/glycine site antagonist, on nociceptive res ponses in the tail flick and formalin tests in mice. Swiss Webster mic e were injected with ACEA-1021 intraperitoneally (1-60 mg/kg), or intr athecally (1-40 mu g/mouse), and tested for antinociception. Systemic administration of ACEA-1021 attenuated the nociceptive responses solel y in the formalin test. Nevertheless, intrathecal administration of AC EA-1021 showed equally potent attenuation of nociceptive responses in both animal models of pain. The effect of ACEA-1021 was also examined on caudally directed biting and scratching (CDBS) behaviors induced by intrathecal administration of NMDA. Microinjections of NMDA (1-1000 m u M) in the spinal cord produced dose-dependent CDBS behaviors. Mice p retreated with ACEA-1021 (0.5-40 mu g/mouse) showed dose-dependent pro tection against CDBS behaviors induced by intrathecal NMDA. Taken toge ther, the results suggest that ACEA-1021 may block spinal NMDA recepto rs to attenuate nociceptive responses, however, our data cannot exclud e the involvement of non-NMDA receptors.