NMDA-coupled periaqueductal gray glycine receptors modulate anxioselective drug effects on plus-maze performance

NMDA-coupled periaqueductal gray glycine receptors modulate anxioselective drug effects on... The present study was carried out to investigate a possible interaction between the effects of anxiety modulating drugs which act at the GABA-A receptor complex and selective N -methyl- d -aspartic acid (NMDA) coupled glycine receptor (GLY-B receptor) ligands within the dorsal periaqueductal gray (DPAG). The plus-maze performance of rats pretreated with diazepam (0.37 and 0.75 mg/kg, i.p.) or pentylenetetrazole (15 and 30 mg/kg, i.p.), standard anxiolytic and anxiogenic drugs respectively, was assessed following intra-periaqueductal injections of either glycine (0.2 M, 0.4 μ l/30 s, i.c.) or its competitive antagonist, 7-chlorokynurenic acid (7ClKYN, 0.02 M, 0.4 μ l/30 s, i.c.). Whilst diazepam produced a typical anxiolytic effect in intracranially-injected CSF rats, increasing open arm exploration, pentylenetetrazole displayed an opposite anxiogenic profile. Either anxiogenic or anxiolytic effects were seen in peripherally-injected vehicle rats following intra-periaqueductal injections of glycine or 7ClKYN, respectively. Intra-periaqueductal injection of glycine markedly attenuated the anxiolytic effect of diazepam. Moreover, while the anxiogenic effects of pentylenetetrazole were barely changed by glycine, they were markedly attenuated by intra-periaqueductal injection of 7ClKYN. Interaction of diazepam and 7ClKYN produced non-selective sedative-like effects which masked any possible anxiolytic action. Accordingly, the present results suggest that the NMDA-coupled glycine receptors located in the DPAG interfere with anxioselective effects of GABA-A acting drugs on the elevated plus-maze. In spite of the prevailing notion that the NMDA coupled glycine receptor is saturated at in vivo brain concentrations of glycine, our results also suggest that either unoccupied or low-affinity GLY-B receptors are likely to be activated by glycine injection into DPAG. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Behavioural Brain Research Elsevier

NMDA-coupled periaqueductal gray glycine receptors modulate anxioselective drug effects on plus-maze performance

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Publisher
Elsevier
Copyright
Copyright © 1998 Elsevier Science B.V.
ISSN
0166-4328
DOI
10.1016/S0166-4328(97)00093-4
Publisher site
See Article on Publisher Site

Abstract

The present study was carried out to investigate a possible interaction between the effects of anxiety modulating drugs which act at the GABA-A receptor complex and selective N -methyl- d -aspartic acid (NMDA) coupled glycine receptor (GLY-B receptor) ligands within the dorsal periaqueductal gray (DPAG). The plus-maze performance of rats pretreated with diazepam (0.37 and 0.75 mg/kg, i.p.) or pentylenetetrazole (15 and 30 mg/kg, i.p.), standard anxiolytic and anxiogenic drugs respectively, was assessed following intra-periaqueductal injections of either glycine (0.2 M, 0.4 μ l/30 s, i.c.) or its competitive antagonist, 7-chlorokynurenic acid (7ClKYN, 0.02 M, 0.4 μ l/30 s, i.c.). Whilst diazepam produced a typical anxiolytic effect in intracranially-injected CSF rats, increasing open arm exploration, pentylenetetrazole displayed an opposite anxiogenic profile. Either anxiogenic or anxiolytic effects were seen in peripherally-injected vehicle rats following intra-periaqueductal injections of glycine or 7ClKYN, respectively. Intra-periaqueductal injection of glycine markedly attenuated the anxiolytic effect of diazepam. Moreover, while the anxiogenic effects of pentylenetetrazole were barely changed by glycine, they were markedly attenuated by intra-periaqueductal injection of 7ClKYN. Interaction of diazepam and 7ClKYN produced non-selective sedative-like effects which masked any possible anxiolytic action. Accordingly, the present results suggest that the NMDA-coupled glycine receptors located in the DPAG interfere with anxioselective effects of GABA-A acting drugs on the elevated plus-maze. In spite of the prevailing notion that the NMDA coupled glycine receptor is saturated at in vivo brain concentrations of glycine, our results also suggest that either unoccupied or low-affinity GLY-B receptors are likely to be activated by glycine injection into DPAG.

Journal

Behavioural Brain ResearchElsevier

Published: Feb 1, 1998

References

  • Role of 5-HT in defensive behavior and anxiety
    Graeff, F.G.
  • Anxiolytic effect on the elevated plus-maze of the NMDA receptor antagonist AP7 microinjected into the dorsal periaqueductal grey
    Guimarães, F.S.; Carobrez, A.P.; De Aguiar, J.C.; Graeff, F.G.
  • Anxiolytic effect of glycine antagonists microinjected into the dorsal periaqueductal grey
    Matheus, M.G.; Nogueira, R.L.; Carobrez, A.P.; Graeff, F.G.; Guimarães, F.S.
  • Role of benzodiazepine receptors located in the dorsal periaqueductal grey in anxiety
    Russo, A.S.; Guimarães, F.S.; De Aguiar, J.C.; Graeff, F.G.
  • Anxiogenic-like effect of glycine and d -serine microinjected into dorsal periaqueductal gray matter of rats
    Schmitt, M.L.; Coelho, W.; Lopes-de-Souza, A.S.; Guimarães, F.S.; Carobrez, A.P.
  • Seizure-triggering mechanisms in the kindling model of epilepsy: collapse of GABA-mediated inhibition and activation of NMDA receptors
    Morimoto, K.
  • Amino acid-mediated regulation of spontaneous synaptic activity patterns in the rat basolateral amygdala
    Smith, B.N.; Dudek, F.E.

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