Chronic inositol increases striatal D-2 receptors but does not modify dexamphetamine-induced motor behavior - Relevance to obsessive-compulsive disorder

A large body of evidence suggests that the neuropathology of obsessive-comp ulsive disorder (OCD) ties in the complex neurotransmitter network of the c ortico-striatal-thalamo-cortical (CSTC) circuit, where dopamine (DA), serot onin (5HT), glutamate (Glu), and gamma-amino butyric acid (GABA) dysfunctio n have been implicated in the disorder. Chronic inositol has been found to be effective; m specific disorders that respond to selective serotonin reup take inhibitors (SSRIs), including OCD, panic, and depression. This selecti ve mechanism of action is obscure. Since nigro-striatal DA tracts are subje ct to 5HT(2) heteroreceptor regulation, one possible mechanism of inositol in OCD may involve its effects on inositol-dependent receptors, especially the 5HT(2) receptor, and a resulting effect on DA pathways in the striatum. In order to investigate this possible interaction, we exposed guinea pigs to oral inositol (1.2 g/kg) for 12 weeks. Subsequently, effects on locomoto r behavior (LB) and stereotype behavior (SB), together with possible change s to striatal 5HT(2) and D-2 receptor function, were determined. In additio n, the effects of chronic inositol on dexamphetamine (DEX)-induced motor be havior were evaluated. Acute DEX (3 mg/kg, ip) induced a significant increa se in both SE and LB, while chronic inositol alone did not modify LA or SE. The behavioral response to DEX was also not modified by chronic inositol p retreatment. However, chronic inositol induced a significant increase in st riatal D-2 receptor density (B-max) with a slight, albeit insignificant, in crease in 5HT(2), receptor density. This suggests that D-2 receptor upregul ation may play an important role in the behavioral effects of inositol alth ough the role of the 5HT(2) receptor in this response is questionable. (C) 2001 Elsevier Science Inc, All rights reserved.