title: Pentobarbital enhances gamma-aminobutyric acid-mediated excitation without altering synaptic plasticity in rat hippocampus.
abstract: BACKGROUND
  Synaptic plasticity is thought to provide a molecular mechanism for learning and memory. N-methyl-d-aspartate receptor-mediated plasticity requires that N-methyl-d-aspartate receptor activation coincides with postsynaptic depolarizing potentials (DPSP(A)'s). Pentobarbital, in high concentrations, enhances DPSP(A)'s, but high concentrations suppress synaptic plasticity, probably by impairing glutamatergic transmission. Here we tested the hypothesis that low concentrations of pentobarbital can enhance DPSP(A)'s and modify the induction of synaptic plasticity.
  
  
  METHODS
  Studies were performed in vitro on rat hippocampal slices. With glutamate transmission blocked, intracellular recording from CA1 neurons was used to investigate the influence of 5 microM pentobarbital on DPSP(A)'s and neuron excitability evoked by high frequency (100 Hz) stimulation. With glutamate transmission intact, extracellular recording was used to examine the effect of 5 microM pentobarbital on the induction of long-term depression and long-term potentiation of synaptic transmission by conditioning stimuli applied to the Schaffer collateral pathway.
  
  
  RESULTS
  High frequency stimulation generated typical DPSP(A)'s that were mediated by gamma-aminobutyric acid(A) receptors and dependent upon HCO3-. Pentobarbital (5 microM) increased the amplitude, but not the width, at half-maximal amplitude of DPSPA's (P < 0.01). Pentobarbital increased the probability of action potential generation during the DPSP(A)'s. Pentobarbital did not alter the induction of long-term depression or long-term potentiation.
  
  
  CONCLUSIONS
  Despite increasing the amplitude of DPSP(A)'s, 5 microM pentobarbital did not alter the induction of synaptic plasticity by a range of conventional conditioning stimuli. These results do not support the hypothesis that excitatory effects of pentobarbital may alter synaptic plasticity.
authors: Department of Anesthesiology, Faculty of Medicine, University of Calgary, Calgary, Canada. david.archer@calgaryhealthregion.ca
authors: David P
authors: DP
authors: Archer
authors: Khanh Q
authors: KQ
authors: Nguyen
authors: Naaznin
authors: N
authors: Samanani
authors: Sheldon H
authors: SH
authors: Roth
mesh_terms: D000759:Adjuvants, Anesthesia / Q000494:pharmacology; D000818:Animals; D001418:Baclofen / Q000031:analogs & derivatives / Q000494:pharmacology; D001639:Bicarbonates / Q000378:metabolism; D001640:Bicuculline / Q000494:pharmacology; D004558:Electric Stimulation; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D018756:GABA Antagonists / Q000494:pharmacology; D018757:GABA Modulators / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects; D009473:Neuronal Plasticity / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010424:Pentobarbital / Q000494:pharmacology*; D051381:Rats; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism; D018080:Receptors, GABA-B / Q000187:drug effects / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects*; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D000759:Adjuvants, Anesthesia; D001639:Bicarbonates; D018756:GABA Antagonists; D018757:GABA Modulators; D011963:Receptors, GABA-A; D018080:Receptors, GABA-B; D005680:gamma-Aminobutyric Acid; D001418:Baclofen; D010424:Pentobarbital; C080629:saclofen; D001640:Bicuculline