Abstract

Pretreatment of mice with a subcutaneous (s.c.) injection of LiCl (1, 3, 10 mmol/kg) 18 h prior to testing produced dose-related attenuation of the reciprocal hindlimb scratching (RHS) response induced by intrathecal (i.t.) administration of pilocarpine. LiCl (10 mmol/kg, 424 mg/kg) pretreatment shifted the pilocarpine (2 µg)-induced RHS dose-response curve about 5-fold to the right compared to vehicle-injected controls (ED<sub>50</sub> = 2.97 and 0.56 µg, respectively). Coadministration of inositol-1,4,5-trisphosphate (IP<sub>3</sub>; 5, 10, 20 µg), but not inositol hexaphosphate (0.03–3 µg), myo-inositol (10 µg) or EDTA (1.33 µg), produced dose-related reversal of the LiCl effect. IP<sub>3</sub> administration alone neither produced RHS nor enhanced the pilocarpine-induced RHS in animals not pretreated with LiCl. These findings provide in vivo evidence for a possible link between RHS and a LiCl-sensitive, possibly phosphoinositide-related, effector pathway.

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