LiCl attenuates M(1)AChR-mediated intrathecal pilocarpine-induced reciprocal hindlimb scratching in mice.
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 microg)-induced RHS dose-response curve about 5-fold to the right compared to vehicle-injected controls (ED(50) = 2.97 and 0.56 microg, respectively). Coadministration of inositol-1,4,5-trisphosphate (IP(3); 5, 10, 20 microg), but not inositol hexaphosphate (0.03-3 microg), myo-inositol (10 microg) or EDTA (1.33 microg), produced dose-related reversal of the LiCl effect. IP(3) 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.
Johnson and Johnson Pharmaceutical Research and Development, L.L.C., Spring House, Pa. 19140, USA.
Rebecca P
RP
Martinez
Robert B
RB
Raffa
D000818:Animals; D006614:Hindlimb; D007278:Injections, Spinal; D007279:Injections, Subcutaneous; D018021:Lithium Chloride / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D051379:Mice; D018721:Muscarinic Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D010716:Phosphatidylinositols / Q000502:physiology; D010862:Pilocarpine / Q000008:administration & dosage / Q000494:pharmacology*; D013239:Stereotyped Behavior / Q000187:drug effects*
D018721:Muscarinic Agonists; D010716:Phosphatidylinositols; D010862:Pilocarpine; D018021:Lithium Chloride