Effect of morphine and naloxone on priming-induced audiogenic seizures in BALB/c mice.
1 Morphine (1-200 mg/kg s.c.) reduced the incidence and prolonged the latency of priming-induced audiogenic siezures in a dose-dependent manner. 2 This effect was reversed by naloxone (1 and 2 mg/kg) although naloxone was itself inactive. 3 This priming-induces seizure model may be useful in the study of tolerance and physical dependence. (+info)
Involvement of tumor necrosis factor alpha and interleukin-1beta in enhancement of pentylenetetrazole-induced seizures caused by Shigella dysenteriae.
Neurologic manifestations, mainly convulsions, are the most frequent extraintestinal complications of shigellosis. We used an animal model to study the roles of tumor necrosis factor alpha (TNF-alpha) and interleukin-1 beta (IL-1beta) in Shigella-related seizures. Administration of Shigella dysenteriae 60R sonicate enhanced the sensitivity of mice to the proconvulsant pentylenetetrazole (PTZ) within 7 h. This was indicated by a significantly higher mean convulsion score and an increased number of mice responding with clonic-tonic seizures in the Shigella-pretreated group. Preinjection of mice with anti-murine TNF-alpha (anti-mTNF-alpha) or anti-murine IL-1beta (anti-mIL-1beta) 30 min prior to administration of Shigella sonicate abolished their enhanced response to PTZ at 7 h. Mean convulsion scores were reduced by anti-mTNF-alpha from 1.2 to 0.8 (P = 0.017) and by anti-mIL-1beta from 1.3 to 0.7 (P = 0.008). Preinjection of anti-mTNF-alpha also reduced the percentage of mice responding with clonic-tonic seizures, from 48 to 29% (P = 0.002), and preinjection of anti-mIL-1beta reduced it from 53 to 21% (P = 0. 012). Neutralization of TNF-alpha or IL-1beta did not protect the mice from death due to S. dysenteriae 60R. These findings indicate that TNF-alpha and IL-1beta play a role in the very early sensitization of the central nervous system to convulsive activity after S. dysenteriae administration. Similar mechanisms may trigger neurologic disturbances in other infectious diseases. (+info)
A correlation between changes in gamma-aminobutyric acid metabolism and seizures induced by antivitamin B6.
The effects of DL-penicillamine (DL-PeA), hydrazine and toxopyrimidine (TXP, 2-methyl-6-amino-5-hydroxymethylpyrimidine) on gamma-aminobutyric acid (GABA) metabolism in mouse brain were studied. All these compounds inhibited the activity of glutamate decarboxylase [EC 188.8.131.52] (GAD) and slightly inhibited that of 4-aminobutyrate: 2-oxoglutarate aminotransferase [EC 184.108.40.206] (GABA-T). In contrast, very different effects were observed on GABA levels; hydrazine caused a marked increase, DL-PeA had no effect, and TXP caused a slight decrease in the content of the amino acid. These results could be described by an equation which related the excitable state to changes in the flux of the GABA bypass. Since the values obtained from the equation clearly reflect the seizure activity, it is suggested that the decreased GABA flux might be a cause of convulsions induced by these drugs. (+info)
NMDA-dependent currents in granule cells of the dentate gyrus contribute to induction but not permanence of kindling.
Single-electrode voltage-clamp techniques and bath application of the N-methyl-D-aspartate (NMDA) receptor antagonist 2-amino-5-phosphonovaleric acid (APV) were used to study the time course of seizure-induced alterations in NMDA-dependent synaptic currents in granule cells of the dentate gyrus in hippocampal slices from kindled and normal rats. In agreement with previous studies, granule cells from kindled rats examined within 1 wk after the last of 3 or 30-35 generalized tonic-clonic (class V) seizures demonstrated an increase in the NMDA receptor-dependent component of the perforant path-evoked synaptic current. Within 1 wk of the last kindled seizure, NMDA-dependent charge transfer underlying the perforant path-evoked current was increased by 63-111% at a holding potential of -30 mV. In contrast, the NMDA-dependent component of the perforant-evoked current in granule cells examined at 2.5-3 mo after the last of 3 or 90-120 class V seizures did not differ from age-matched controls. Because the seizure-induced increases in NMDA-dependent synaptic currents declined toward control values during a time course of 2.5-3 mo, increases in NMDA-dependent synaptic transmission cannot account for the permanent susceptibility to evoked and spontaneous seizures induced by kindling. The increase in NMDA receptor-dependent transmission was associated with the induction of kindling but was not responsible for the maintenance of the kindled state. The time course of alterations in NMDA-dependent synaptic current and the dependence of the progression of kindling and kindling-induced mossy fiber sprouting on repeated NMDA receptor activation are consistent with the possibility that the NMDA receptor is part of a transmembrane signaling pathway that induces long-term cellular alterations and circuit remodeling in response to repeated seizures, but is not required for permanent seizure susceptibility in circuitry altered by kindling. (+info)
A new X linked neurodegenerative syndrome with mental retardation, blindness, convulsions, spasticity, mild hypomyelination, and early death maps to the pericentromeric region.
We report on a family with an X linked neurodegenerative disorder consisting of mental retardation, blindness, convulsions, spasticity, and early death. Neuropathological examination showed mild hypomyelination. By linkage analysis, the underlying genetic defect could be assigned to the pericentromeric region of the X chromosome with a maximum lod score of 3.30 at theta=0.0 for the DXS1204 locus with DXS337 and PGK1P1 as flanking markers. (+info)
Modulation of phosphatidylinositol turnover on central nicotinic receptors.
AIM: To study the modulatory effects of phosphatidylinositol (PI) turnover on nicotinic receptors in CNS, and to study the relationship between brain nicotinic receptors and PI turnover. METHODS: Effects of inositol phosphatase inhibitor lithium chloride (LiCl) and muscarinic receptor agonist oxotremorine (Oxo) on nicotine-induced convulsions were investigated in mice. RESULTS: The effects of nicotine for producing convulsions were modified by LiCl 2.5-10 mmol.kg-1, revealing the convulsive effects of nicotine > 0.8 mg.kg-1 were increased by acute pretreatment with LiCl rather than oxotremorine. Mice were given LiCl 5.0 mmol.kg-1 once a day for 7 d, the ED50 value of nicotine for producing convulsions was increased from 0.58 to 0.97 mg.kg-1, suggesting that the sensitivity of central nicotinic receptors for mediating convulsions was decreased by chronic treatment with LiCl. CONCLUSION: The functions of central nicotinic receptors were modulated by PI turnover. (+info)
Determination of the lipophilicity of active anticonvulsant N-substituted amides of alpha-arylalkylamine-gamma-hydroxybutyric acid.
The lipophilicities of fourteen anticonvulsant active N-substituted amides of alpha-arylalkylamine-gamma-hydroxybutyric acid [I-XIV] have been determined by reversed-phase thin-layer chromatography with a mixture of methanol, TRIS buffer, and acetic acid as the solvent system. The RM value of each compound decreased linearly with increasing concentration of methanol. The partition coefficients (log P) of the amides were calculated by use of the Prolog P module of the Pallas system. Comparison of RM and log P enabled clog P values to be calculated. It was found that the anticonvulsant activity of amides [I-XIV] can be explained on the basis of their lipophilicity. (+info)
Synthesis and anticonvulsant activity of 1,2-aminoalkanol derivatives.
A series of 1,2-aminoalkanol derivatives were prepared and evaluated for anticonvulsant activity in the maximal electroshock seizure (MES) and subcutaneous pentylenetetrazole seizure threshold (scMet) assays and for neurotoxicity (TOX). Most interesting were the anticonvulsant results of S-(+)-2-amino-1-butanol derivative VIII, which displayed anti-MES activity with a protective index (TD50/ED50) of 4.55 corresponding with that for phenytoin, carbamazepine and valproate. (+info)