Elsevier

Biological Psychiatry

Volume 31, Issue 5, 1 March 1992, Pages 505-514
Biological Psychiatry

Inositol triphosphate, cyclic AMP, and cyclic GMP in rat brain regions after lithium and seizures

https://doi.org/10.1016/0006-3223(92)90261-WGet rights and content

Abstract

The mechanism of action of lithium, the primary treatment for bipolar affective disorder, is unknown but may involve inhibition of second messenger production in the brain. Therefore, the concentrations of three second messengers, inositol 1,4,5 triphosphate (Ins 1,4,5P3), cyclic adenosine monophosphate (AMP), and cyclic guanosine monophosphate (GMP), were measured in rat cerebral cortex and hippocampus after acute or chronic lithium administration, as well as after treatment with the cholinergic agonist pilocarpine alone or in combination with lithium at a dose that induces seizures only in lithium pretreated rats. Neither acute nor chronic lithium treatment altered the hippocampal or cortical concentration of Ins 1,4,5P3, cyclic AMP, or cyclic GMP. Pilocarpine administered alone increased Ins 1,4,5P3 in both regions, did not alter cyclic AMP, and slightly increased cyclic GMP in the cortex. Coadministration of lithium plus pilocarpine caused large increases in the concentrations of all three second messengers and the production of each of them was uniquely attenuated: lithium reduced pilocarpine-induced increases of Ins 1,4,5P3 in the cortex at 60 min; chronic lithium administration reduced stimulated cyclic AMP production in the hippocampus; and chronic lithium treatment impaired stimulated cyclic GMP production in both regions. In summary, chronic lithium treatment appeared only to reduce Ins 1,4,5P3 and cyclic AMP concentrations after a long period of stimulation whereas cyclic GMP production was reduced by chronic lithium administration after both short and long periods of stimulation. Thus cyclic GMP was most sensitive to lithium and lithium attenuation of second messenger formation may be most important in excessively activated pathways.

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    This work was supported by NIMH grant MH38752 and by the U.S. Army medical Research and Development Command under contract No. DAMD17-89-C-9037. Opinions, interpretations, and recommendations are those of the authors and are not necessarily endorsed by the U.S. Army. In conducting research using animals, the investigators adhered to the Guide for the Care and Use of Laboratory Animals prepared by the Committee on Care and Use of Laboratory Animals of the Institute of Laboratory Animal Resources, National Research Council.

    The authors thank Dot McAdory for manuscript preparation.

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