Tiagabine antinociception in rodents depends on GABAB receptor activation: parallel antinociception testing and medial thalamus GABA microdialysis
| Autor: | Alessandra Ipponi, Claudia Lamberti, Petra Malmberg-Aiello, Alessandro Bartolini, Antonio Medica |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
Male
Pain Threshold Baclofen Microdialysis Tiagabine Narcotic Antagonists Nipecotic Acids Pain Constriction Pathologic (+)-Naloxone Pharmacology GABAB receptor GABA Antagonists Mice chemistry.chemical_compound Organophosphorus Compounds Thalamus Escape Reaction Abdomen medicine Noxious stimulus Animals Neurotransmitter Uptake Inhibitors GABA Agonists gamma-Aminobutyric Acid Pain Measurement Dose-Response Relationship Drug Naloxone Antagonist Nociceptors Nociception Receptors GABA-B chemistry Extracellular Space Psychomotor Performance CGP-35348 medicine.drug |
| Zdroj: | European Journal of Pharmacology. 368:205-211 |
| ISSN: | 0014-2999 |
| DOI: | 10.1016/s0014-2999(99)00034-5 |
| Popis: | The effects of a new antiepileptic drug, tiagabine, (R)-N-[4,4-di-(3-methylthien-2-yl)but-3-enyl] nipecotic acid hydrochloride, were studied in mice and rats in antinociceptive tests, using three kinds of noxious stimuli: mechanical (paw pressure), chemical (abdominal constriction) and thermal (hot plate). In vivo microdialysis was performed in parallel in awake, freely moving rats in order to evaluate possible alterations in extracellular gamma-aminobutyric acid (GABA) levels in a pain-modulating region, the medial thalamus. Systemic administration of tiagabine, 30 mg kg(-1) i.p., increased nearly twofold the extracellular GABA levels in rats and increased significantly the rat paw pressure nociceptive threshold in a time-correlated manner. Dose-related significant tiagabine-induced antinociception was also observed at the doses of 1 and 3 mg kg(-1) i.p. in the mouse hot plate and abdominal constriction tests. The tiagabine antinociception was completely antagonised by pretreatment with the selective GABA(B) receptor antagonist, CGP 35348, (3-aminopropyl-diethoxy-methyl-phosphinic acid) (2.5 microg/mouse or 25 microg/rat i.c.v.), but not by naloxone (1 mg kg(-1) s.c.), both administered 15 min before tiagabine. Thus, it is suggested that tiagabine causes antinociception due to raised endogenous GABA levels which in turn activate GABA(B) receptors. |
| Databáze: | OpenAIRE |
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