Biomedical subjects

Andrzej Pilc

Publications and source records attributed to Andrzej Pilc.

9 recordsLinked to original sources

PubMed2003

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 (11.5 mgZn/kg), all: acute, sub-chronic and chronic administration, reduced the immobility time in the FST in rats. Removal of olfactory bulbs (OB surgery) in rats is associated with variety of behavioral abnormalities such as deficit in a step-down passive avoidance or hyperactivity in the "open field" test. Both acute and chronic administration of zinc hydroaspartate reduced the number of trials needed to the learning passive avoidance and reduced the OB-induced hyperactivity in rats. At the time schedule following zinc hydroaspartate administration, when behavioral experiments were performed, the serum zinc concentrations were significantly higher than control-physiological values. These results confirm activity of zinc in the FST, show its antidepressant-like activity in the OB rat model of depression, demonstrate the lack of tolerance to these effects and suggest relationship of these antidepressant-like effects with the rise in serum zinc. These animal data further suggest antidepressant activity of zinc in human depression.

Animals↗

PubMed2003

LY-354740 (Eli Lilly).

Lilly is developing LY-354740, the lead compound in a series of derivatives of the metabotropic glutamate receptor group II agonist L-CCG-1, for the potential treatment of anxiety [212536], [276941], [276942].

Animals↗

PubMed2002

Inhibitory effects of MPEP, an mGluR5 antagonist, and memantine, an N-methyl-D-aspartate receptor antagonist, on morphine antinociceptive tolerance in mice.

RATIONALE: Inhibition of N-methyl- D-aspartate (NMDA) receptors by memantine, an NMDA-receptor antagonist, and other antagonists of ionotropic receptors for glutamate inhibit the development of opiate antinociceptive tolerance. The role of metabotropic receptors for glutamate (mGluR) in opiate tolerance is less known. OBJECTIVE: In the present study, we examined the effect of 2-methyl-6-(phenylethynyl)-pyridine (MPEP), the mGluR type-I (subtype mGluR5) antagonist, as well as the effect of co-administration of low doses of memantine and MPEP on morphine antinociceptive tolerance in mice. METHODS: Morphine antinociceptive activity was tested twice, before and after chronic morphine administration, in the tail-flick test using a cumulative dose-response protocol. Tolerance was induced by six consecutive days of b.i.d. administration of morphine (10 mg/kg, s.c.). Saline, memantine (7.5 mg/kg and 2.5 mg/kg, s.c.), MPEP (30 mg/kg and 10 mg/kg, i.p.) and the combination of both antagonists at low doses was given 30 min prior to each morphine injection during its chronic administration. A separate experiment assessed the effects of memantine, MPEP and their combination on acute morphine antinociception using a tail-flick test. RESULTS: MPEP (30 mg/kg but not 10 mg/kg) as well as memantine (7.5 mg/kg but not 2.5 mg/kg) attenuated the development of tolerance to morphine-induced antinociception. When given together, the low doses of MPEP (10 mg/kg) and memantine (2.5 mg/kg) also significantly attenuated opiate tolerance. None of the treatments with glutamate antagonists produced antinociceptive effects or significantly affected morphine-induced antinociception. CONCLUSIONS: The data suggest that both mGluR5 and NMDA receptors may be involved in the development of morphine antinociceptive tolerance.

Analgesics, Opioid↗

PubMed2002

The striatum as a target for anti-rigor effects of an antagonist of mGluR1, but not an agonist of group II metabotropic glutamate receptors.

The aim of the present study was to find out whether the metabotropic receptor 1 (mGluR1) and group II mGluRs, localized in the striatum, are involved in antiparkinsonian-like effects in rats. Haloperidol (1 mg/kg ip) induced parkinsonian-like muscle rigidity, measured as an increased resistance of a rat's hind foot to passive flexion and extension at the ankle joint. (RS)-1-aminoindan-1,5-dicarboxylic acid (AIDA; 0.5-15 microg/0.5 microl), a potent and selective mGluR1 antagonist, or (2R,4R)-4-aminopyrrolidine-2,4-dicarboxylate (2R,4R-APDC; 7.5-15 microg/0.5 microl), a selective group II agonist, was injected bilaterally into the striatum of haloperidol-treated animals. AIDA in doses of 7.5-15 microg/0.5 microl diminished the haloperidol-induced muscle rigidity. In contrast, 2R,4R-APDC injections were ineffective. The present results may suggest that the blockade of striatal mGluR1, but not the stimulation of group II mGluRs, may ameliorate parkinsonian muscle rigidity.

Animals↗

PubMed2002

Group II mGlu receptor agonists inhibit behavioural and electrophysiological effects of DOI in mice.

It has been suggested that metabotropic glutamate (mGlu) receptor agonists selective for Group II mGlu receptors may have antipsychotic action. Therefore, we studied whether the effects, which could be related to psychotomimetic action of hallucinogenic drugs, are inhibited by Group II mGlu receptor agonists. The selective mGlu2/3 agonists LY354740 and LY379268 inhibited (+/-)1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI)-induced head twitches in mice in a dose-dependent manner. Furthermore, LY379268 suppressed an increase in the frequency of spontaneous excitatory synaptic potentials induced by bath-applied DOI in layer V pyramidal cells recorded in the murine medial frontal cortex. The data indicate that Group II mGlu receptor agonists may counteract the effects of hallucinogenic drugs.

Amino Acids↗

PubMed2002

[Not Available].

Explore the source record for details and available documents.

Journal Article↗

PubMedDate not supplied

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. Since glutamatergic transmission is controlled not only by ionotropic but also by metabotropic glutamate receptors (mGluR), their involvement in the etiology and the therapy of depression was also postulated. Recent studies, showing that antidepressant treatment may influence mGlu receptors, together with the findings that group I mGluR antagonists, may possess antidepressant-like action, support this hypothesis.

Animals↗

PubMedDate not supplied

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. The present study investigated the interaction of zinc with antidepressants in the forced swimming test in mice. Mice were injected with imipramine or citalopram alone and in combination with zinc. Low, ineffective per se doses of imipramine and citalopram administered together with low, ineffective doses of zinc were active in this test. The present data support the notion that inhibition of the NMDA receptor participates in an antidepressant action, and further demonstrate particular role of zinc in this activity.

Animals↗

PubMedDate not supplied

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.

Animals↗