The expression of nitric oxide synthase mRNA and the enzyme activity were studied in the hippocampus of rats treated with lithium chloride (LiCl; 12 mEqkg-1 i.p.) and tacrine (5 mgkg-1 i.p.). In comparison to vehicle treated animals, mRNA signal was augmented by 2-fold 24 h after administration of LiCl and by 4-fold 15 min after tacrine. In LiCl pretreated rats, tacrine yielded a 6-fold mRNA increase and this was prevented by corticosterone (35 mgkg-1, given i.p. 30 min before tacrine). Combined administration of LiCl and tacrine also produced an approx. 80% increase in Ca(2+)-calmodulin-dependent nitric oxide synthase activity. The present results represent the first demonstration that in the hippocampus mRNA expression of constitutive brain nitric oxide synthase can be augmented with consequent increase in nitric oxide synthesis.