Biphasic effect of acamprosate on NMDA but not on GABAA receptors in spontaneous rhythmic activity from the isolated neonatal rat respiratory network
| Autor: | Olivier Pierrefiche, Mickaël Naassila, Martine Daoust |
|---|---|
| Přispěvatelé: | Groupe de Recherche sur l'alcool et les pharmacodépendances - UMR INSERM_S 1247 (GRAP), Université de Picardie Jules Verne (UPJV)-Institut National de la Santé et de la Recherche Médicale (INSERM), Naassila, Mickael |
| Jazyk: | angličtina |
| Rok vydání: | 2004 |
| Předmět: |
Aging
Hypoglossal Nerve N-Methylaspartate MESH: Rats Taurine Acamprosate MESH: Alcohol Deterrents MESH: Rats Sprague-Dawley Pharmacology Inhibitory postsynaptic potential Receptors N-Methyl-D-Aspartate MESH: Animals Newborn Rats Sprague-Dawley 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine medicine Animals MESH: Aging MESH: Animals [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] Receptor MESH: Receptors GABA-A 030304 developmental biology 0303 health sciences MESH: Receptors N-Methyl-D-Aspartate Chemistry GABAA receptor Receptors GABA-A 3. Good health Rats MESH: Taurine MESH: N-Methylaspartate Mechanism of action Animals Newborn nervous system MESH: Hypoglossal Nerve Excitatory postsynaptic potential Respiratory Mechanics NMDA receptor MESH: Respiratory Mechanics [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] Brainstem medicine.symptom 030217 neurology & neurosurgery medicine.drug Alcohol Deterrents |
| Zdroj: | Neuropharmacology Neuropharmacology, Elsevier, 2004, 47 (1), pp.35-45. ⟨10.1016/j.neuropharm.2004.03.004⟩ Neuropharmacology, 2004, 47 (1), pp.35-45. ⟨10.1016/j.neuropharm.2004.03.004⟩ |
| ISSN: | 0028-3908 |
| DOI: | 10.1016/j.neuropharm.2004.03.004⟩ |
| Popis: | International audience; Acamprosate (calcium acetylhomotaurinate) has been shown to be effective in attenuating relapse in human alcoholics. The precise mechanism for acamprosate has been yet to be determined as there may be multiple sites of action for this drug. We investigated the mechanism of action of acamprosate on a spontaneous rhythmic activity recorded from hypoglossal nerve rootlet (XII) in neonatal rat brainstem slices. At 30 microM, acamprosate reversibly increased burst amplitude and reduced burst frequency, whereas at higher concentrations (100-400 microM) it induced a reversible and concentration-dependent inhibition of this activity. Interestingly, acamprosate (30 microM) enhanced the effects of low NMDA-induced excitation (1.5 microM), but inhibited higher NMDA-induced excitation (2.5, 5 microM) by 50-70%, demonstrating a differential effect on NMDA-induced excitation. Blockade of GABAA receptors did not affect the increase in amplitude of 30 microM acamprosate and partially abolished the inhibitory effects of 200 microM acamprosate. At 200 microM, acamprosate reduced high NMDA-induced excitation and abolished NMDA-evoked excitatory tonic phase, suggesting that excitatory effect of low concentrations of acamprosate mainly involved NMDA receptors, while the inhibitory effects at higher concentration included an increase in GABAA-mediated inhibition with a reduction of NMDA-mediated excitation. Consequently, combined blockade of both receptors abolished all effects of acamprosate tested at all concentrations. These results show that the effects of acamprosate are mediated via both GABAA and NMDA receptors and suggest a partial co-agonist role on NMDA receptors, at the level of a spontaneously active network. |
| Databáze: | OpenAIRE |
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