5-HT EFFLUX FROM RAT HIPPOCAMPUS IN-VIVO PRODUCED BY 4-AMINOPYRIDINE IS INCREASED BY CHRONIC LITHIUM ADMINISTRATION

EFFECTS Of lithium on central 5-HT function have been shown using elec trophysiological, behavioural and neurochemical approaches. Chronic li thium administration, for example, enhances both electrophysiological and behavioural responses mediated by postsynaptic 5-HT1A receptors as well as increasing potassium-evoked and electrically evoked release o f 5-HT from the hippocampus and in vitro slices and in vivo. Our studi es have shwon that potassium-channel blocking drugs increase 5-HT rele ase in vivo, and others have shown that lithium suppresses potassium c urrents in some cell types. We therefore investigated in the rat the e ffect of short-term (3-days) and long-term (21 days) lithium on 5-HT r elease evoked by potassium-channel blockade, using in vivo microdialys is. Long-term lithium treatment enhanced 5-HT efflux in rat hippocampu s produced by 4-aminopyridine (4-AP) perfused in microdialysis fluid b y as much as 100% within 40 min, compared with non-lithium-treated con trol rats. Short-term lithium treatment did not enhance 4-AP-induced 5 -HT efflux. The effect of local tetraethylammonium chloride (TEA) on h ippocampal 5-HT release was unaltered by long-term lithium treatment. In addition, neither the effect of local perfusion with 4-AP on efflux of striatal 5-HT, or dopamine in nucleus accumbens, was altered by ch ronic lithium treatment. These results show that long-term lithium tre atment enhances 4-AP-stimulated efflux of 5-HT in the hippocampus, but not in the striatum, nor dopamine output in the nucleus accumbens. It is suggested that chronic lithium treatment may enhance the sensitivi ty of voltage sensitive potassium-channels to 4-AP in the rat hippocam pus and thereby cause more 5-HT to be released by 4-AP-induced potassi um-channel blockade.