Myo-inositol attenuates the enhancement of the serotonin syndrome by lithium

Lithium elicits opposite effects on two behavioural syndromes in rats: enhancement of the 5-HT_1A-linked serotonin syndrome and attenuation of the 5-HT₂-linked wet dog shakes. The ability of intracerebroventricular (ICV)myo-inositol or forskolin to reverse the enhancement of the serotonin syndrome by lithium was tested in rats that were fed chronic dietary lithium or control diet and injected with the serotonin agonist 5-MeODMT (5-methoxy-N, N-dimethyltryptamine). Lithium enhanced the total serotonin syndrome score and particularly flat posture and tremor. Inositol, but not forskolin, mitigated the effects of lithium. Inositol was also injected in the lateral ventricle of rats pretreated with chronic dietary lithium or regular rat chow for 3 weeks and injected with carbidopa and l-5-hydroxytryptophan (5-HTP). Lithium attenuated wet dog shakes, but inositol had no significant effect on lithium-treated or control rats. These findings suggest that the enhancement of the serotonin syndrome by lithium may be related to lithium-induced inositol depletion.