Circadian variation in rat brain AP-1 DNA binding activity after cholinergic stimulation: modulation by lithium

The potential influence of a circadian rhythm and its modulation by lithium on the stimulation of AP-1 DNA binding activity by the cholinergic agonist pilocarpine was investigated in rat cerebral cortex. Stimulation of AP-1 binding after pilocarpine (30 mg/kg) was evident within 1 h and was maximally stimulated by 200% at 2 h. Pilocarpine-stimulated AP-1 binding exhibited a circadian rhythm in AP-1 binding measured at 0800, 1200, and 1600 hours, 2 h after pilocarpine. Pilocarpine-stimulated AP-1 binding at 0800 hours was approximately twice the level measured at 1600 hours. After acute lithium treatment, pilocarpine administration induced generalized seizures after about 20 min and stimulated AP-1 binding which increased continuously for 4.5 h, at which time the stimulation was 900% above control. A circadian variation was apparent in AP-1 binding stimulated by acute lithium plus pilocarpine, with stimulation at 0800 hours being 1.5 times that at 1600 hours. After chronic lithium and pilocarpine, which also produced seizures, there was no circadian variation in pilocarpine-stimulated AP-1 binding. Thus pilocarpine-induced AP-1 binding in rat cerebral cortex was influenced by a circadian rhythm, but this was abolished by chronic lithium administration.