Antidepressant-like activity of 8-Br-cAMP, a PKA activator, in the forced swim test.

The PKA activator, 8-Br-cAMP, dose-dependently reduced the immobility time in the forced swim test in rats. This effect was antagonized by co-treatment with selective PKA inhibitor Rp-cAMPS. This is the first demonstration of the antidepressant-like activity of the PKA activator.

Chronic imipramine treatment reduces inhibitory properties of group II mGlu receptors without affecting their density or affinity.

An increasing body of evidence indicates an important role of the glutamatergic system in the pathophysiology of depression. Not only ionotropic but also metabotropic glutamate receptors (mGlu receptors) have been suggested to be involved in the mechanism of action of antidepressant drugs. Moreover, several mGlu receptor ligands possess a great antidepressant potential.

Citalopram influences mGlu7, but not mGlu4 receptors' expression in the rat brain hippocampus and cortex.

Earlier studies showed that chronic electroconvulsive shock (ECS) or imipramine treatment induced a sub-sensitivity of group I metabotropic glutamate receptors (mGluRs) in the hippocampus as well as an increase in the receptor protein level in this structure. In the present study, the effects of chronic imipramine (10 mg/kg, 21 days) or citalopram (10 mg/kg, 21 days) treatment on the mGlu4 or mGlu7 receptors' protein levels in the frontal cortex and hippocampus of the rat brain were examined using the Western blot analysis. We also examined the influence of these drugs' administration on forskolin-stimulated cAMP formation.

Activation of the mGlu7 receptor elicits antidepressant-like effects in mice.

Rationale: Broad evidence indicates that modulation of the glutamatergic system could be an efficient way to achieve antidepressant activity. Metabotropic glutamate receptor (mGlu receptor) ligands seem to be promising agents to treat several central nervous system disorders, including psychiatric ones.

Objectives: The aim of our study was to investigate potential antidepressant-like activity of the first, selective, and bio-available mGlu7 receptor agonist, AMN082 (N,N'-dibenzyhydryl-ethane-1,2-diamine dihydrochloride), in wild-type (WT) and mGlu7 receptor knock-out (KO) mice.

Metabotropic glutamate receptor ligands as possible anxiolytic and antidepressant drugs.

Depression and anxiety represent a major problem. However, the current treatment of both groups of diseases is not satisfactory. As the glutamatergic system may play an important role in pathophysiology of both depression and anxiety, we decided to discuss the recent data on possible anxiolytic and/or antidepressant effects of metabotropic glutamate (mGlu) receptor ligands.

Are compounds acting at metabotropic glutamate receptors the answer to treating depression?

Numerous studies over the last few years have suggested that modulating the glutamatergic system may be an efficient method to achieve an antidepressant effect. Data suggest that metabotropic glutamate receptors (mGlu receptors), related to long-term, modulatory effects on glutamatergic neurotransmission, may be a good target for the development of new, effective and safe therapeutic drugs to treat several CNS disorders including depression and anxiety. Several potent, selective and systemically active orthosteric and allosteric ligands of specific mGlu receptor subtypes have been discovered and these have been tested as potential antidepressants in models of depression in rodents.

Anxiolytic action of group II and III metabotropic glutamate receptors agonists involves neuropeptide Y in the amygdala.

Several lines of evidence indicate that activation of group II and III metabotropic glutamate (mGlu) receptors produces anxiolytic-like effects in rodents. On the other hand neuropeptide Y (NPY) induces an anxiolytic effect in rats after intraventricular or intraamygdalar administration. Therefore, in the present study we investigated whether the anxiolytic action of (2S,3S,4S)-(carboxycyclopropyl)glycine (L-CCG-I), an mGlu2/3 receptor agonist, and (1S,3R,4S)-1-aminocyclopentane-1,3,4-tricarboxylic acid (ACPT-1), an mGluR4/6/7/8 receptor agonist, was mediated by a mechanism involving NPY receptor.

Potential antidepressant-like effect of MTEP, a potent and highly selective mGluR5 antagonist.

The involvement of glutamate in the pathophysiology of depression has been suggested by a number of experiments. It was well established that compounds, which decreased glutamatergic transmission via blockade of NMDA receptor, produced antidepressant-like action in animal tests and models. The present study was carried out to investigate whether a selective mGluR5 antagonist 3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]-pyridine (MTEP) induces antidepressant-like effects after intraperitoneal injections in male Wistar rats or male C57BL/6J mice.

Selective mGlu5 receptor antagonist MTEP attenuates naloxone-induced morphine withdrawal symptoms.

Several lines of evidence suggest a crucial involvement of glutamate in the mechanism of drug addiction. The involvement of group I mGlu receptors in the mechanism of addiction has also been proposed. Given the recent discovery of selective and brain penetrable mGlu5 receptor antagonists, the effects of 3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]-pyridine (MTEP) were evaluated in the naloxone-precipitated morphine withdrawal model.

Involvement of CRF but not NPY in the anxiety regulation via NMDA receptors.

The study attempts to evaluate whether neuropeptide Y (NPY) and corticotropin-releasing factor (CRF) are involved in anxiogenic and anxiolytic reactions induced by NMDA receptor ligands. The animals were given MK-801 (1 mg/kg, ip), a non-competitive NMDA-receptor antagonist, which acts as anxiolytic agent, or NMDA (15 mg/kg, ip), which has an anxiogenic effect. The anxiogenic or anxiolytic actions of these compounds were evaluated in the plus-maze test.

In the amygdala anxiolytic action of mGlu5 receptors antagonist MPEP involves neuropeptide Y but not GABAA signaling.

Several lines of evidence indicate that inhibition of the metabotropic glutamate (mGlu) receptor 5 produces anxiolytic-like effects in rodents. Peptide neurotransmitter neuropeptide Y (NPY) produces an anxiolytic effect in rats after intraventricular or intra-amygdalar administration. Many classes of anxiolytic drugs exert their effect through the GABA-benzodiazepine (BZD) receptor complex.

Anxiolytic- and antidepressant-like effects of group III metabotropic glutamate agonist (1S,3R,4S)-1-aminocyclopentane-1,3,4-tricarboxylic acid (ACPT-I) in rats.

We examined the anxiolytic-like activity of (1S,3R,4S)-1-aminocyclopentane-1,3,4-tricarboxylic acid (ACPT-I) using the Vogel conflict drinking test, while antidepressant-like effects of this compound were evaluated using Porsolt's test. ACPT-I, a selective group III mGlu receptor agonist, produced a dose-dependent anticonflict effect after intrahippocampal injections and antidepressant-like effect in rats after intraventricular injections. These data suggest that selective group III mGlu receptor agonists may become a new class of anxiolytics and/or antidepressants.

Interaction of zinc with antidepressants in the forced swimming test in mice.

Recent preclinical data have suggested that glutamate NMDA receptor may be involved in the mechanism of action of antidepressant treatments. Functional antagonists of the NMDA receptor complex exhibit an antidepressant-like effect in animal tests that predict antidepressant activity and in animal models of depression. Zinc, a very potent inhibitor of the NMDA receptor, is active in the forced swimming test in rats and mice.

On the role of metabotropic glutamate receptors in the mechanisms of action of antidepressants.

Most conventional antidepressant drugs influence serotoninergic, adrenergic, and/or dopaminergic systems, increasing serotonin, norepinephrine and dopamine synaptic availability. More recently attention has focused on glutamatergic system. Both preclinical and clinical studies, showing antidepressant-like actions of compounds which reduce transmission at N-methyl-D-aspartate (NMDA) receptors, indicate possible involvement of glutamatergic system in the etiology of depression.

Antidepressant-like effects of acute and chronic treatment with zinc in forced swim test and olfactory bulbectomy model in rats.

The activity of zinc administered intraperitoneally, acutely (in single dose), sub-chronically (in triple doses) or chronically (once daily for 14 days) were assessed in the forced swim test (FST) and olfactory bulbectomy (OB) model of depression in rats. Previously, we have demonstrated that acute administration of zinc sulfate is active in FST in rats and mice. In the present study, zinc hydroaspartate in a dose of 65 mg/kg (11.