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In our previous paper we reported that droperidol, one of butyrophenones, acts by occupying GABA receptors and exerting a GABA-like effect on the postsynaptic membrane of GABA-operated synapses, while chlorpromazine, one of phenothiazines, apparently does not have such an action (1). The present work was an attempt to provide further evidence for a GABA-like effect of droperidol. We investigated the interaction between droperidol or chlorpromazine and imidazole acetic acid which is known to act on the same group of receptors as GABA (2-4), or glycine which is reported to depress the firing rate of Purkinje cells in the cat cerebellum (5, 6). Experiments were carried out on 34 adult cats anesthetized with pentobarbital sodium (40 mg/kg, i.p.). The surgical procedures and recording and analysis of data were essen tially the same as those in our previous experiment (1). Single units were recorded ex tracellularly from spontaneously firing Purkinje cells in the superficial folia of the cerebellar vermis and drugs were administered microiontophoretically at the site of recording through 3-, or 6-barreled micropipettes (with 2.5-7.5 /im tip diameters). Drugs used were as follows: droperidol (7 mM, pH 4.2, tartaric acid; Janssen); chlorpromazine HC1 (50 mM in 150 mM NaCl, pH 5.4; Merck); imidazole acetic acid (0.5 M, pH 3.2, NaOH; Sigma); glycine (1 M, pH 3.2, HCI; Sigma); bicuculline (5 mM in 165 mM NaCI, pH 3.2, HC1; Pierce). All these drug solutions were ejected with a positive current and the ejection time was 10 sec. Ex tracellular action potentials were recorded on an audiotape for later processing by a PDP-12 computer. All Purkinje cells recorded in the present experiments were sensitive to GABA ejected with 5-80 nA. First, interaction between droperidol and imidazole acetic acid (IAA) was examined in 22 Purkinje cells. IAA (more than 30 nA) and droperidol (more than 40 nA) depressed the spontaneous firing in 18 and 14 of 22 Purkinje cells, respectively; IAA in 4 cells and droperidol in 8 cells did not produce any significant action, or it was difficult to distinguish a possible depression due to IAA or droperidol from a spontaneous variation of the firing frequency. A comparison of the action of IAA and droperidol on the same cell

FURTHER ELECTROPHYSIOLOGICAL EVIDENCE FOR THE GABA-LIKE EFFECT OF DROPERIDOL IN THE PURKINJE CELLS OF THE CAT CEREBELLUM1