Lithium affects REM sleep occurrence, autonomic activity and brain second messengers in the rat

The effects of a single intraperitoneal administration of lithium, a drug used to prevent the recurrence of mania in bipolar disorders, were determined in the rat by studying changes in: (i) the wake–sleep cycle; (ii) autonomic parameters (hypothalamic and tail temperature, heart rate); (iii) the capacity to accumulate cAMP and IP3 in the preoptic-anterior hypothalamic region (PO-AH) and in the cerebral cortex (CC) under an hypoxic stimulation at normal laboratory and at low ambient temperature (Ta). In the immediate hours following the injection, lithium induced: (i) a significant reduction in REM sleep; (ii) a non-significant reduction in the delta power density of the EEG in NREM sleep; (iii) a significant decrease in the concentration of cAMP in PO-AH at normal laboratory Ta; (iv) a significant increase of IP3 concentration in CC following exposure to low Ta. The earliest and most sensitive effects of lithium appear to be those concerning sleep. These changes are concomitant with biochemical effects that, in spite of a systemic administration of the substance, may be differentiated according to the second messenger involved, the brain region and the ambient condition.