IONTOPHORESIS OF LI+ ANTAGONIZES NORADRENERGIC SYNAPTIC INHIBITION OF RAT CEREBELLAR PURKINJE-CELLS

Li salts provide effective therapy for manic-depressive psychosis, but the site and mechanism of this effect are not known. We have tested the ability of Li, applied by microiontophoresis, to modify the responsiveness of rat cerebellar Purkinje neurons to iontophoretic applications of norepinephrine and γ-aminobutyrate and to the inhibition produced by stimulation of the noradrenergic ceruleo-cerebellar pathway. As previously reported for rat hippocampal neurons, acute exposure to Li produces selective, reversible antagonism of the effects of norepinephrine and the noradrenergic pathway but does not affect inhibitory actions of γ-aminobutyrate. Collectively, these selective antagonisms of noradrenergic synaptic inhibitions in the cerebellum and hippocampus man indicate a general effect of Li suitable for extended observations in rats exposed to Li for the chronic periods needed to achieve therapeutic effects in man.