Abstract
1, 2-Benzisoxazole-3-acetamidoxime hydrochloride (PF-257) was found to have a potentiating effect on the β-(3, 4-dihydroxyphenyl)-L-alanine response in addition to the imipramine-like effect on behaviors in rodents. In the present experiments, the effects on the caudate spindle and additional several responses of PF-257 were examined to clarify the mode of action of the compound on the central dopaminergic system. In gallamine-immobilized cats, PF-257 depressed the caudate spindle in a dose of 5 mg/kg, i.v. which changed the spontaneous electroencephalographic (EEG) arousal patterns to the drowsy ones and had little or no effect on the EEG arousal response induced by stimulation of the sciatic nerve. With 5 mg/kg which caused the EEG changes, PF-257 facilitated both recruiting response and cortical focal seizure elicited by stimulation of the thalamus and visual cortex, respectively. With 10 mg/kg, acceleration of the spontaneous EEG arousal patterns, facilitation of the EEG arousal response, and biphasic actions on both recruiting response and caudate spindle were observed. From these results, it seems possible to conclude that PF-257 has one of sites of action in the caudate nucleus and the depression of this nucleus by the compound probably results in the increased susceptibility of the thalamo-cortical region.
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