The group III mGlu receptor agonist ACPT-I exerts anxiolytic-like but not antidepressant-like effects, mediated by the serotonergic and GABA-ergic systems.
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.
Stachowicz
K
K
Institute of Pharmacology, Polish Academy of Sciences, Smetna 12, 31-343 Krakow, Poland.
Kłodzińska
A
A
Palucha-Poniewiera
A
A
Schann
S
S
Neuville
P
P
Pilc
A
A
D000818:Animals; D014151:Anti-Anxiety Agents / Q000008:administration & dosage / Q000494:pharmacology*; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000494:pharmacology; D001007:Anxiety / Q000188:drug therapy; D003517:Cyclopentanes / Q000008:administration & dosage / Q000494:pharmacology*; D003863:Depression / Q000188:drug therapy; D005442:Flumazenil / Q000494:pharmacology; D058787:GABA-A Receptor Antagonists; D007274:Injections, Intraperitoneal; D008297:Male; D010879:Piperazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists*; D016713:Ritanserin / Q000494:pharmacology; D012701:Serotonin / Q000378:metabolism*; D058829:Serotonin 5-HT1 Receptor Antagonists; D058830:Serotonin 5-HT2 Receptor Antagonists; D012702:Serotonin Antagonists / Q000494:pharmacology; D013315:Stress, Psychological / Q000150:complications / Q000188:drug therapy*; D014233:Tricarboxylic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
C108242:1-aminocyclopentane-1,3,4-tricarboxylic acid; D014151:Anti-Anxiety Agents; D000928:Antidepressive Agents; D003517:Cyclopentanes; D058787:GABA-A Receptor Antagonists; D010879:Piperazines; D011725:Pyridines; D018094:Receptors, Metabotropic Glutamate; D058829:Serotonin 5-HT1 Receptor Antagonists; D058830:Serotonin 5-HT2 Receptor Antagonists; D012702:Serotonin Antagonists; D014233:Tricarboxylic Acids; D016713:Ritanserin; D012701:Serotonin; D005442:Flumazenil; D005680:gamma-Aminobutyric Acid; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide