The effect of chronic lithium treatment on serotonergic neurotransmission

The effect of chronic lithium treatment on [3H]5-HT release and its regulation by presynaptic mechanisms was studied in [3H]5-HT preloaded superfused rat cortical, hippocampal and hypothalamic slices. The data indicate that long-term but not acute lithium administration (1) increases Ca2+-dependent. 65 mM K+-evoked [3H]5-HT efflux in the three brain areas examined, (2) induces a decrease in spontaneous [3H]5-HT efflux in the cortex and hypothalamus and with an increase in basal hippocampal 5-HT efflux, (3) depresses the maximal functional capacity of presynaptic serotonin autoreceptors, and (4) profoundly inhibits protein skinase C-mediated potentiation of both K+-evoked and basal [3H]5-HT efflux. The mechanism underlying lithium's effect on protein kinase C-related function was further investigated. The results indicate that PMA (phorbol 12-myristate, 13-acetate) increased protein kinase C translocation from cytosol to membrane-bound fractions. Following the activation of protein kinase C by PMA, the levels of immunoprecipitated MAPs, TAU and α-tubulin, were found to be increased