LY354740, a potent group II metabotropic glutamate receptor agonist prevents lactate-induced panic-like response in panic-prone rats

Anantha Shekhar, S. R. Keim

Research output: Contribution to journalArticle

103 Citations (Scopus)

Abstract

LY354740 is a potent and selective agonist at the group II metabotropic glutamate receptors and is shown to be an effective inhibitor of glutamate release with significant anxiolytic and drug withdrawal alleviating properties in certain animal models. Rats with chronic inhibition of GABA synthesis in the dorsomedial hypothalamus (DMH) are highly anxious and exhibit panic-like responses to peripheral lactate infusions similar to patients with panic disorder. Using these panic-prone rats, we tested the efficacy of LY354740 in preventing the lactate-induced panic-like response, comparing it to alprazolam, a clinically effective anti-panic drug. Rats were fitted with femoral arterial and venous catheters and implanted with Alzet pumps infusing the GABA synthesis inhibitor L-allylglycine into the DMH. After four days of recovery, they were confirmed to be panic-prone to lactate infusions as indicated by increases in heart rate, blood pressure, respiratory rate and 'anxiety' measured in the social interaction test. Next, they were pretreated with either vehicle, LY354740 (0.3 and 0.6 mg/kg) or alprazolam (0.5 and 1.0 mg/kg) and re-challenged with lactate infusions. LY354740 treatment was equally efficacious as alprazolam in preventing lactate-induced panic attacks in this model. These data suggest that LY354740 could be a novel anti-panic drug, as effective as alprazolam in acute treatment. Copyright (C) 2000 Elsevier Science Ltd.

Original languageEnglish
Pages (from-to)1139-1146
Number of pages8
JournalNeuropharmacology
Volume39
Issue number7
DOIs
StatePublished - Jun 2000

Fingerprint

eglumetad
Excitatory Amino Acid Agonists
Panic
Metabotropic Glutamate Receptors
Alprazolam
Lactic Acid
Panic Disorder
gamma-Aminobutyric Acid
Hypothalamus
Allylglycine
Pharmaceutical Preparations
Anti-Anxiety Agents
Interpersonal Relations
Respiratory Rate
Thigh
Glutamic Acid
Catheters
Anxiety
Animal Models
Heart Rate

Keywords

  • Alprazolam
  • Anxiety
  • Dorsomedial nucleus
  • GABA
  • Glutamate
  • Hypothalamus
  • Social interaction
  • Stress

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Drug Discovery
  • Pharmacology

Cite this

LY354740, a potent group II metabotropic glutamate receptor agonist prevents lactate-induced panic-like response in panic-prone rats. / Shekhar, Anantha; Keim, S. R.

In: Neuropharmacology, Vol. 39, No. 7, 06.2000, p. 1139-1146.

Research output: Contribution to journalArticle

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