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ANESTHETIC PHARMACOLOGY

Pentobarbital Enhances -Aminobutyric Acid-Mediated Excitation Without Altering Synaptic Plasticity in Rat Hippocampus

David P. Archer, MD^*, Khanh Q. Nguyen, MSc^*, Naaznin Samanani, BSc^*, and Sheldon H. Roth, PhD^*

From the Department of *Anesthesiology, Clinical Neurosciences, and Pharmacology and Therapeutics, Faculty of Medicine, University of Calgary, Calgary, Canada.

Address correspondence to David P. Archer, MD, Department of Anesthesiology, Foothills Medical Center, 1403 29th St, Calgary, Alberta, Canada T2N 2T9. Address e-mail to david.archer{at}calgaryhealthregion.ca.

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 µM 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 µM 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 -aminobutyric acid_A receptors and dependent upon HCO₃^–. Pentobarbital (5 µM) 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 µM 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.

This article has been cited by other articles:

				D. Archer and S. Roth Anesthetics are exciting! Implications of pharmacologically-induced nociceptive hyperreflexia/Les anesthesiques, c'est excitant... Implications de l'hyperreflectivite nociceptive provoquee par pharmacologie Can J Anesth, January 1, 2008; 55(1): 6 - 10. [Full Text] [PDF]

Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999