- Inositol, a precursor for membrane phosphoinositides involved in signal transduction, has been found to be clinically effective in a number of psychiatric disorders and to reverse behavioural effects of lithium. To gain insight into the mechanism of action of inositol, it is critical to establish its efficacy in animal models. Following the initial report by Cohen et al. (1997b) that inositol was anxiolytic in the elevated plus maze model of anxiety, the effect of chronic intraperitoneal and chronic dietary inositol administration in rats was tested in four experiments. There was a significant increase in closed arm and total arm entries following chronic injection of inositol, but no effect of inositol when it was given chronically in rat chow. Because the first 2 experiments suggested that the mode of drug administration affected the control levels of anxiety (open arm entries and time in open arms) in control groups, the effect of chronic dietary inositol was tested in rats that were exposed to a mild and a more severe form of stress. Chronic saline injections elevated anxiety in the plus maze, which was only marginally affected by chronic dietary inositol. Following 3 weeks administration of 5% dietary inositol rats were pre-exposed to a cat. There was a clear in-crease in number of entries into open arms, suggesting an anxiolytic effect of inositol.