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ANESTHETIC PHARMACOLOGY

Small-Dose Pentobarbital Enhances Synaptic Transmission in Rat Hippocampus

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

Departments of *Anesthesia and Pharmacology and Therapeutics, University of Calgary, Calgary, Alberta, Canada

Address correspondence and reprint requests to David P. Archer, MD, Department of Anesthesia, Foothills Medical Centre, 1403 29th Street N.W., Calgary, Alberta, Canada T2N 2T9. Address e-mail to archerd{at}cadvision.com

We investigated the contribution of bicarbonate ion, -aminobutyric acid-A (GABA_A) receptors, and N-methyl-D-aspartate (NMDA) receptors to pentobarbital-induced enhancement of excitatory synaptic transmission in the hippocampal slice. Transverse hippocampal slices (400 µm thick) were prepared from 20- to 30-day-old Sprague-Dawley rats and maintained in an interface chamber perfused with warmed (35°C) oxygenated artificial cerebrospinal fluid. Extracellular field potentials, evoked by orthodromic paired-pulse stimulation of the Schaffer collateral CA1 pathway, were analyzed for the population spike (PS) amplitude. Pentobarbital had a concentration-dependent, biphasic effect on PS amplitudes, which were increased approximately twofold (P < 0.001) when the slice was exposed to pentobarbital concentrations of 1 and 5 µM and depressed at drug concentrations larger than 10 µM. Pentobarbital (5 µM) did not increase the PS amplitude when stimulation was stopped during exposure to the drug. The enhancement of PS amplitude was suppressed in the presence of 10 µM acetazolamide, a nonselective carbonic anhydrase inhibitor, and when the slice was bathed in CO₂/HCO₃^--free artificial cerebrospinal fluid. Pretreatment with 1 µM picrotoxin, a GABA_A receptor antagonist, or 5 µM 2-amino-5-phosphopentanoic acid, a specific NMDA receptor antagonist, also suppressed enhancement of PS amplitude by 5 µM pentobarbital. The results suggest that small concentrations of pentobarbital (1 and 5 µM) enhance synaptic transmission through mechanisms involving GABA_A and NMDA receptors and the HCO₃^- ion.

IMPLICATIONS: Enhanced hippocampal synaptic transmission after exposure to subanesthetic concentrations of pentobarbital persists during drug washout. This finding may help to explain why some patients experience excitation and enhanced pain during emergence from anesthesia.

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