These results are in compliance with findings that seizures can be generated in AT, MS, PRC, and PPC by means of nerve agents, chemoconvulsants, or kindling. Results from microinfusion studies show that anticonvulsant efficacy is obtained by GABA(A) modulators or cholinergic antagonists (M1-M5) in AT, cholinergic antagonists (M1-M5) in MS, combined glutamatergic (NMDA) and cholinergic antagonist (M1-M4), AMPA antagonist, or modulators of metabotropic glutamate receptors (mGluR5, mGluR2/3) in PRC, and cholinergic
antagonist (M1-M5) or GABAA agonist in PPC. Calculation of impact factors for the most potent drugs (percentage of positive effects in the seizure controlling sites) showed that scopolamine and procyclidine were ranking highest (75) followed by muscimol (50), NBQX (33), and caramiphen (33). Potential strategies for prophylactic and GSK923295 cell line post-exposure treatments are discussed. (C) 2010 Elsevier Inc. All rights reserved.”
“Manganese (Mn) accumulation in the brain has been shown to alter the neurochemistry
of the basal ganglia. Mn-induced alterations Selleckchem GSK-J4 in dopamine biology are fairly well understood, but recently more evidence has emerged characterizing the role of gamma-aminobutyric acid (GABA) in this dysfunction. The purpose of this study was to determine if the previously observed Mn-induced increase in extracellular GABA (GABA(EC)) was due to altered GABA transporter
(GAT) function, and whether Mn perturbs other amino acid neurotransmitters, namely taurine and glycine (known modulators of GABA). Extracellular GABA, taurine, and glycine concentrations were collected from the striatum of control (CN) or Mn-exposed Levetiracetam Sprague-Dawley rats using in vivo microdialysis, and the GAT inhibitor nipecotic acid (NA) was used to probe GAT function. Tissue and extracellular Mn levels were significantly increased, and the Fe:Mn ratio was decreased 36-fold in the extracellular space due to Mn-exposure. NA led to a 2-fold increase in GABA(EC) of CNs, a response that was attenuated by Mn. Taurine responded inversely to GABA, and a novel 10-fold increase in taurine was observed after the removal of NA in CNs. Mn blunted this response and nearly abolished extracellular taurine throughout collection. Striatal taurine transporter (Slc6a6) mRNA levels were significantly increased with Mn-exposure, and Mn significantly increased (3)H-Taurine uptake after 3-min exposure in primary rat astrocytes. These data suggest that Mn increases GABA(EC) by inhibiting the function of GAT, and that perturbed taurine homeostasis potentially impacts neural function by jeopardizing the osmoregulatory and neuromodulatory functions of taurine in the brain. (C) 2010 Elsevier Inc. All rights reserved.