The effects of acute and chronic lithium treatment on pilocarpine‐stimulated phosphoinositide hydrolysis in mouse brain in vivo

1 Measurements were made of the in vivo formation of inositol phosphates in the brains of C57/B1/601a mice treated acutely or chronically with lithium chloride (LiCl). 2 A single injection of LiCl (10 m Equiv kg−1, s.c.) 18 h before death increased the accumulation of [3H]‐inositol phosphates ([3H]‐Ins P's) in the brains of mice injected i.c.v. with [3H]‐myo‐inositol 24 h previously. 3 Pilocarpine (200 mg kg−1, i.p.) injected 15 min before death further enhanced the formation of [3H]‐Ins P's in the brains of LiCl‐treated, but not saline‐treated, mice. The enhancement due to pilocarpine was abolished by injection of atropine sulphate (10 mg kg−1, i.p.) 10 min earlier. 4 Chronic (14 days) LiCl feeding produced an accumulation of [3H]‐Ins P's significantly less than that due to a single injection of LiCl, but the response to pilocarpine was markedly greater in mice chronically fed with LiCl when compared with mice acutely injected with LiCl. 5 Mass measurements of endogenous inositol 1,4,5 triphosphate revealed increases due to pilocarpine and chronic LiCl feeding alone. A combination of the two treatments produced levels greater than either alone. 6 These results demonstrate that LiCl treatment enhances both basal and pilocarpine‐stimulated inositol phospholipid hydrolysis in vivo and this might be relevant to its therapeutic effects.