EFFECTS OF CHRONIC LITHIUM TREATMENT ON AGONIST-ENHANCED EXTRACELLULAR CONCENTRATIONS OF CYCLIC-AMP IN THE DORSAL HIPPOCAMPUS OF FREELY MOVING RATS

Studies on brain slices and homogenates suggest that chronic lithium t reatment affects the activity of adenylate cyclases in the brain. To i nvestigate whether chronic lithium administration influences the cycli c AMP (cAMP) synthesis in vivo, we have used microdialysis to assess l ithium-induced alterations in extracellular concentrations of cAMP in the dorsal hippocampus of freely moving rats. Local infusion of noradr enaline or forskolin through the microdialysis probes produced rapid i ncreases in the extracellular concentrations of cAMP in the dorsal hip pocampus. Lithium administration for 4 weeks (serum lithium concentrat ion of 0.8 +/- 0.11 mmol/L) did not affect the baseline levels of cAMP . However, in rats fed a lithium-supplemented diet, noradrenaline- and forskolin-induced enhancement of cAMP levels was decreased in the dor sal hippocampus. The rats were videotaped 18 min before and 27 min aft er initiating the introduction of noradrenaline and forskolin into the dorsal hippocampus. The infusion of agonists induced a moderate behav ioral excitation. Rats treated with lithium were less active compared with the control rats. Taken together, these data confirm that chronic lithium administration affects the cAMP signaling system in the brain of living animals, presumably by interfering with a site beyond the r eceptor level.