Abstract
Our earlier studies have demonstrated that (1S,3R,4S)-1-aminocyclo-pentane-1,3,4-tricarboxylic acid ACPT-I, a group III mGlu receptor agonist, produced anxiolytic-like and antidepressant-like actions after central administration. Here we describe the anxiolytic-like effects of ACPT-I after intraperitoneal administration in the stress-induced hyperthermia (SIH), elevated plus-maze (PMT) tests in mice and in the Vogel test in rats. However, the compound did not produce antidepressant-like effects in the tail suspension test (TST) or in the forced swim test (FST) in mice. The potential anxiolytic effect of ACPT-I (20 mg/kg) in the SIH test was inhibited by the benzodiazepine receptor antagonist flumazenil (given i.p., 10 mg/kg), and by a 5-HT(1A) receptor antagonist N-{2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl}-N-(2-pyridynyl) cyclohexane-carboxamide (WAY100635) (0.1 mg/kg s.c.). At the same time, ritanserin (0.5 mg/kg i.p.), the 5-HT2A/C receptor antagonist, did not change the anxiolytic-like effects of ACPT-I. The results of these studies indicate that the GABA-ergic and serotonergic systems are involved in the potential anxiolytic action of ACPT-I.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Anti-Anxiety Agents / administration & dosage
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Anti-Anxiety Agents / pharmacology*
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Antidepressive Agents / administration & dosage
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Antidepressive Agents / pharmacology
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Anxiety / drug therapy
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Cyclopentanes / administration & dosage
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Cyclopentanes / pharmacology*
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Depression / drug therapy
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Flumazenil / pharmacology
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GABA-A Receptor Antagonists
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Injections, Intraperitoneal
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Male
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Piperazines / pharmacology
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Pyridines / pharmacology
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Rats
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Rats, Wistar
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Receptors, Metabotropic Glutamate / agonists*
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Ritanserin / pharmacology
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Serotonin / metabolism*
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Serotonin 5-HT1 Receptor Antagonists
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Serotonin 5-HT2 Receptor Antagonists
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Serotonin Antagonists / pharmacology
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Stress, Psychological / complications
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Stress, Psychological / drug therapy*
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Tricarboxylic Acids / administration & dosage
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Tricarboxylic Acids / pharmacology*
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gamma-Aminobutyric Acid / metabolism*
Substances
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1-aminocyclopentane-1,3,4-tricarboxylic acid
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Anti-Anxiety Agents
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Antidepressive Agents
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Cyclopentanes
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GABA-A Receptor Antagonists
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Piperazines
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Pyridines
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Receptors, Metabotropic Glutamate
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Serotonin 5-HT1 Receptor Antagonists
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Serotonin 5-HT2 Receptor Antagonists
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Serotonin Antagonists
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Tricarboxylic Acids
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Ritanserin
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Serotonin
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Flumazenil
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gamma-Aminobutyric Acid
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N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide