Differential modulatory actions of GABA_A agonists on susceptibility to GABA_A antagonists-induced seizures in morphine dependent rats: Possible mechanisms in seizure propensity

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• 作者：Siyavash Joukar^a ; ^b ; ^c ; ^{sjokar@gmail.com"" rel=""nofollow} ; ^{jokar@kmu.ac.ir"" rel=""nofollow} ; Nafiseh Atapour^a ; Tajpari Kalantaripour^d ; Hamideh Bashiri^e ; Alireza Shahidi^b
• 关键词：Morphine-dependence ; GABA_A agonists ; Seizure ; GABA_A receptor
• 刊名：Pharmacology Biochemistry and Behavior
• 出版年：2011
• 出版时间：July 2011
• 年：2011
• 卷：99
• 期：1
• 页码：17-21
• 全文大小：282 K

文摘

In order to clarify the mechanisms involved in the susceptibility to GABA_A antagonists-induced seizures in morphine dependent rats, we investigated how GABA_A agonists modulate this vulnerability. Seizures were induced to animals by infusion of GABA_A antagonists: pentylenetetrazole (PTZ), picrotoxin (PIC) and bicuculline (BIC). GABA_A agonists, muscimol (MUS) and 4,5,6,7-tetrahydroisoxazolo [5,4-c]pyridin-3-ol (THIP), were administered intravenous (i.v.) before antagonists. Morphine-dependence significantly decreased the PTZ threshold dose (19.16 ± 1.89 versus 25.74 ± 1.25 mg/kg) while, it had no effect on PIC induced seizures. BIC doses for both threshold and tonic–clonic seizures induction were significantly lower in morphine dependent rats (0.10 ± 0.01 and 0.12 ± 0.02 versus 0.25 ± 0.02 and 0.39 ± 0.07 mg/kg respectively). In morphine-dependence, although pre-treatment with MUS significantly increased the required dose of PTZ for seizures threshold, THIP significantly decreased the required dose of PTZ for tonic–clonic convulsion. Moreover, MUS pretreatment completely recovered the effect of morphine dependency on BIC seizure activity.

The results suggest that the capability of GABA_A agonists on modulation of propensity to seizures induced by different antagonists in morphine-dependence is dissimilar. Therefore, it seems that long-term morphine alters some properties of GABA system so that the responsive rate of GABA_A receptors not only to its antagonists, but also to its agonists will change differently.