title: Differential modulatory actions of GABAA agonists on susceptibility to GABAA antagonists-induced seizures in morphine dependent rats: possible mechanisms in seizure propensity.
abstract: 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±1.25mg/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±0.07mg/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.
authors.affiliation: Neuroscience Research Center, Kerman University of Medical Sciences, Kerman, Iran. sjokar@gmail.com
authors.forename: Siyavash
authors.initials: S
authors.lastname: Joukar
authors.forename: Nafiseh
authors.initials: N
authors.lastname: Atapour
authors.forename: Tajpari
authors.initials: T
authors.lastname: Kalantaripour
authors.forename: Hamideh
authors.initials: H
authors.lastname: Bashiri
authors.forename: Alireza
authors.initials: A
authors.lastname: Shahidi
mesh_terms: D000818:Animals; D018755:GABA Agonists / Q000494:pharmacology* / Q000627:therapeutic use; D018756:GABA Antagonists / Q000633:toxicity*; D008297:Male; D009021:Morphine Dependence / Q000503:physiopathology*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D011963:Receptors, GABA-A / Q000502:physiology*; D012640:Seizures / Q000139:chemically induced* / Q000503:physiopathology* / Q000517:prevention & control
chemical_list: D018755:GABA Agonists; D018756:GABA Antagonists; D011963:Receptors, GABA-A