The inositol monophosphatase inhibitor L-690,330 affects pilocarpine-behavior and the forced swim test.
BACKGROUND
Lithium has been a standard pharmacological treatment for bipolar disorder over the last 60 years; however, the molecular targets through which lithium exerts its therapeutic effects are still not defined. Attenuation of the phosphatidylinositol signal transduction pathway as a consequence of inhibition of inositol monophosphatase (IMPase) has been proposed as one of the possible mechanisms for lithium-induced mood stabilization.


OBJECTIVE
The objective was to study the behavioral effect of the specific competitive IMPase inhibitor L-690,330 in mice in the lithium-sensitive pilocarpine-induced seizures paradigm and the forced swim test (FST).


METHODS
The inhibitor was administered intracerebroventricularly in liposomes.


RESULTS
L-690,330 increased the sensitivity to subconvulsive doses of pilocarpine and decreased immobility time in the FST.


CONCLUSIONS
It is possible that the behavioral effects of lithium in the pilocarpine-induced seizures and in the FST are mediated through the inhibition of IMPase, but reversal of the inhibitor's effect with intracerebroventricular inositol would be an important further step in proof.
Department of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
Liza
L
Shtein
Lilach
L
Toker
Yuly
Y
Bersudsky
R H
RH
Belmaker
Galila
G
Agam
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D004164:Diphosphonates / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D007276:Injections, Intraventricular; D008081:Liposomes; D008094:Lithium / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010744:Phosphoric Monoester Hydrolases / Q000037:antagonists & inhibitors*; D010862:Pilocarpine / Q000494:pharmacology*; D012640:Seizures / Q000139:chemically induced / Q000201:enzymology / Q000523:psychology; D015398:Signal Transduction; D013550:Swimming
D014150:Antipsychotic Agents; D004164:Diphosphonates; D008081:Liposomes; D010862:Pilocarpine; C079103:L 690330; D008094:Lithium; D010744:Phosphoric Monoester Hydrolases; C021822:myo-inositol-1 (or 4)-monophosphatase