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SMALL CONCENTRATIONS OF PENTOBARBITAL INCREASE NEURONAL EXCITABILITY IN RAT HIPPOCAMPUS BY ENHANCING GABA_ARECEPTOR-MEDIATED DEPOLARIZATION.

Department of Anesthesia, University of Calgary, Calgary, Alberta, Canada T2N 2T9

INTRODUCTION

Small concentrations of pentobarbital enhance synaptic transmission in the stratum radiatum-CA1 pathway of rat hippocampus (1). The cellular mechanism of the latter effect remains unknown. Here we have used intracellular recording techniques to directly examine the influence of small concentrations of pentobarbital on post-synaptic GABA_A receptor-mediated excitatory depolarizing responses.

METHODS

Protocols were approved by the Faculty of Medicine Animal Care Committee. Experiments were performed in vitro using hippocampal slices prepared from male Sprague Dawley rats as previously described (1). The membrane potentials of individual CA1 neurons were recorded with a sharp microelectrode inserted intracellularly. Responses to stimulation of the stratum radiatum pathway were evaluated during perfusion of the slice with artificial cerebrospinal fluid. GABA_A receptor-mediated depolarization was evoked by bursts of 4 stimuli (frequency 100 Hz, 20 V) applied to a tungsten electrode inserted approximated 15mm from the intracellular electrode(2). Excitatory glutamatergic transmission was blocked with 50 µM AP-5 and 10 µM CNQX. Depolarizing responses were quantified by the maximal amplitude of the depolarization, and its duration as shown by the time of the maximal response (T_max) and the time of the half-return to baseline (T_50%max).

RESULTS

Stimulation of the stratum radiatum pathway in the presence of glutamate receptor blockade produced a biphasic potential consisting of an initial hyperpolarization, (5 mV, 75 msec duration) followed by a longer depolarizing response (characteristics summarized in the Table). The biphasic potential was abolished by the addition of 100 µM picrotoxin, consistent with GABA_A receptor mediated depolarization (2). Thirty minutes of exposure to 5 µM pentobarbital increased both the amplitude and duration of the depolarizing response (Table).

The present results support the hypothesis that pentobarbital facilitates synaptic transmission in hippocampal pathways through enhancement of GABA_A receptor-mediated postsynaptic depolarization.

REFERENCES

1 Anesth Analg 93:1521–5

2 J Neurosci 19: 9252–60

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