Effects of lithium and haloperidol administration on the rat brain levels of substance P.

In an attempt to obtain more biochemical information concerning the possible roles of substance P (SP) in the etiology of mental and neurological disorders, we studied the effects of long-term administration of lithium or haloperidol on the levels of this peptide in various rat brain regions. Daily injections of LiCl (5 mEq/kg/day for 6 days) increased the SP level in regions which are enriched in dopamine innervation such as striatum, nucleus accumbens or frontal cortex, but not in the other regions such as hypothalamus, hippocampus or brain stem. Subchronic oral administration of Li2CO3 through the diet also caused a time-dependent increase in striatal SP level which was prevented by coadministration with haloperidol. This result suggests that the dopaminergic system might mediate the change in SP level elicited by lithium.