Pr op. Neur r r Psychophor maccd 6 zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA Biol Psychtat. 1983. Vol. 7. pp. 821-325 Printed in G reat Brttain. All rtght~ reserved. zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA BIPHASIC ACI’IONS zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA SHELDON H. zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFE OF PFXUTOBARBITAL ON ROTH' , BRIAN H. BLAND' and 027~ 5846183 $0.00 + .50 Copyrisht 0 1983 Pergamon Press Ltd. SYNAPTIC TRANSMISSION BRUCE M. MACIVER' Departments of 'Pharmacology & Therapeutics and 'Psychology, University of Calgary, Calgary, Alberta, Canada. (Final form, July 1983) Abstract H. Bland and Bruce M. MacIver; Biphasic actions of pentobarbital Prog. Neuro-Psychopharmacol. & Biol. Psychiat. 1983,7(4-6) 1. The effects of pentobarbital were studied on hippocampal slice preparation. 2. Low concentrations of oentobarbital (0.04 - 0.1 Schaffer collateral to CA I evoked EPSP and population 3. Higher concentrations of pentobarbital (0.2 - 1.0 potential amplitudes. synaptic transmission in the rat mM) produced an increase in the field potential amplitudes. mM) produced depression of field 4. Pentobarbital altered synaptic transmission by affecting both pre- and post-synaptic functions. 5. Analysis of input/output curves suggest the presynaptic site is most sensitive. Keywords: pentobarbital, hippocampal slice, synaptic transmission, anesthetics. Abbreviations: Schaffer collateral (SCH); commissural (COMM); excitatory post-synaptic potential (EPSP); cerebral spinal fluid (CSF). Introduction zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPO It has been well documented that anaesthetic barbiturates can inhibit excitatory transmission and enhance inhibitory transmission (see Ho and Harris, 1981; Richards, 1983). Slight structural modification can also lead to changes in activity which cannot be explained by differences in lipid solubility (Ho and Harris, 1981). Furthermore, some barbiturates have been shown to produce concentration-dependent biphasic (excitatory/depressant) actions on Johnston, 1978). neuronal membrane excitability (e.g. phenobarbital; It can be suggested that barbiturates act at more than one site and perhaps via different mechanisms. Previous studies in our laboratory have demonstrated a biphasic (excitatory/depressant) action of pentobarbital on membrane electrical properties of a single isolated neuron (MacIver and Roth, 1980). The present study was undertaken to determine whether similar biphasic effects are produced on synaptic transmission in the mammalian central nervous system. The effects of pentobarbital were studied on the well characterized Schaffer collateral to CA 1 synaptic pathway in rat hippocampal slice preparations. 821