The Putative AMPA Receptor Antagonist, LY326325, Produces Anxiolytic-Like Effects Without Altering Locomotor Activity in Rats

The Putative AMPA Receptor Antagonist, LY326325, Produces Anxiolytic-Like Effects Without... Anxiolytic-like effects produced by the novel, water-soluble AMPA/kainate receptor antagonist, LY326325 (3RS,4aRS,6RS,8aRS)-6-(2-(1(2)H-tetrazole-5-yl)ethyl)decahydro-isoquinoline-3-carboxylic acid), were examined in the elevated plus-maze and in a conflict-suppressed drinking situation. Administration of low doses (0.5, 1, 2, and 5 mg/kg; IP, −30 min) of LY326325 to Sprague–Dawley rats did not alter the percentage of entries into the open arms of the plus-maze, whereas only one dose of LY326325 (1 mg/kg) produced a slight, but significant, increase of the time spent in the open arms of the plus maze. In the conflict-suppressed drinking test, similar doses of LY326325 (2.5 and 5 mg/kg; IP, −30 min) caused a dose-dependent and significant increase of punished drinking behavior without having any significant effects on unpunished drinking. The anxiolytic-like effects of LY326325 in the plus-maze and in the anticonflict tests were observed at doses, which, by themselves, had no influence on various measures of locomotor activity, i.e., horizontal activity, forward locomotion, and corner time. Our data suggest that the putative AMPA/glutamate receptor antagonist, LY326325, produces anxiolytic-like effects similar to those of diazepam in the conflict-suppressed drinking test, but displays considerably weaker anxiety-reducing properties compared to diazepam in the elevated plus-maze. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Pharmacology Biochemistry and Behavior Elsevier

The Putative AMPA Receptor Antagonist, LY326325, Produces Anxiolytic-Like Effects Without Altering Locomotor Activity in Rats

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Publisher
Elsevier
Copyright
Copyright © 1998 Elsevier Science Inc.
ISSN
0091-3057
eISSN
1873-5177
DOI
10.1016/S0091-3057(97)00565-0
Publisher site
See Article on Publisher Site

Abstract

Anxiolytic-like effects produced by the novel, water-soluble AMPA/kainate receptor antagonist, LY326325 (3RS,4aRS,6RS,8aRS)-6-(2-(1(2)H-tetrazole-5-yl)ethyl)decahydro-isoquinoline-3-carboxylic acid), were examined in the elevated plus-maze and in a conflict-suppressed drinking situation. Administration of low doses (0.5, 1, 2, and 5 mg/kg; IP, −30 min) of LY326325 to Sprague–Dawley rats did not alter the percentage of entries into the open arms of the plus-maze, whereas only one dose of LY326325 (1 mg/kg) produced a slight, but significant, increase of the time spent in the open arms of the plus maze. In the conflict-suppressed drinking test, similar doses of LY326325 (2.5 and 5 mg/kg; IP, −30 min) caused a dose-dependent and significant increase of punished drinking behavior without having any significant effects on unpunished drinking. The anxiolytic-like effects of LY326325 in the plus-maze and in the anticonflict tests were observed at doses, which, by themselves, had no influence on various measures of locomotor activity, i.e., horizontal activity, forward locomotion, and corner time. Our data suggest that the putative AMPA/glutamate receptor antagonist, LY326325, produces anxiolytic-like effects similar to those of diazepam in the conflict-suppressed drinking test, but displays considerably weaker anxiety-reducing properties compared to diazepam in the elevated plus-maze.

Journal

Pharmacology Biochemistry and BehaviorElsevier

Published: May 1, 1998

References

  • Effects of ethanol, chlordiazepoxide, and MK-801 on performance in the elevated-plus maze and on locomotor activity
    Criswell, H.E.; Knapp, D.H.; Overstreet, D.H.; Breese, G.R.
  • Lack of effect of L-687,414 ((+)- cis -4-methyl-HA-966), an NMDA receptor antagonist acting at the glycine site, on cerebral glucose metabolism and cortical neuronal morphology
    Hargreaves, R.J.; Rigby, M.; Smith, D.; Hill, R.G.
  • Cloned glutamate receptors
    Hollmann, M.; Heinemann, S.
  • Evidence for an anxiogenic action of AMPA receptor antagonists in the plus-maze test
    Karcz-Kubicha, M.; Liljequist, S.
  • Decreased experimental anxiety and voluntary ethanol consumption in rats following central but not basolateral amygdala lesions
    Möller, C.; Wiklund, L.; Sommer, W.; Thorsell, A.; Heilig, M.
  • MK-801 produces antianxiety effect in the elevated plus-maze in mice
    Sharma, A.C.; Kulkarni, S.K.
  • Effects of site-selective NMDA receptor antagonists in an elevated plus-maze model of anxiety in mice
    Wiley, J.L.; Cristello, A.F.; Balster, R.L.

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