Tiagabine antinociception in rodents depends on GABAB receptor activation: parallel antinociception testing and medial thalamus GABA microdialysis
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- 作者：Ipponi ; Alessandra ; Lamberti ; Claudia ; Medica ; Antonio ; Bartolini ; Alessandro ; Malmberg-Aiello ; Petra
- 关键词：Tiagabine ; Antinociception ; Microdialysis ; GABA (γ ; -aminobutyric acid) ; GABAB receptor ; Medial thalamus
- 刊名：European Journal of Pharmacology
- 出版年：1999
- 出版时间：March 5, 1999
- 年：1999
- 卷：368
- 期：2-3
- 页码：205-211
- 全文大小：213 K
文摘
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 γ-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 GABAB receptor antagonist, CGP 35348, (3-aminopropyl-diethoxy-methyl-phosphinic acid) (2.5 μg/mouse or 25 μg/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 GABAB receptors.