Letter - Epi-inositol is ineffctive in Porsolt Forced Swim Test model of depression

Alona Shaldubina¹, Haim Einat², Yuly Bersudsky¹, RH Belmaker¹

¹Stanley Center for Bipolar Research, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel; ²College of Pharmacy, University of Minnesota–Duluth, Duluth, MN, USA

The six-carbon polyol inositol is a uniquely versatile compound in biology. Myo-inositol is the major naturally occurring isomer of nine possible inositol isomers and is critical for the phosphoinositide (PI) cycle as a substrate for PI synthase (Berridge and Irvine 1989). Benjamins and Agranoff (1969) reported that epi-inositol is not a substrate for PI synthase, but a number of experiments suggest that epi-inositol might affect the PI cycle. Like myo-inositol, epi-inositol was shown to reverse Li-pilocarpine seizures (Williams and Jope 1995), strongly suggesting that epiinositol could enter the PI cycle. Furthermore, accumulation of [3H]-cytidine monophosphate phosphatidate (CMP-PA) in Chinese hamster ovary (CHO) cells during Li treatment is reversible with myo-inositol, and Richards and Belmaker (1996) found that epi-inositol was about 30%–40% as active as myo-inositol in reversing such accumulation. Myoinositol has been found to have antidepressant and antianxiety effects in animal models (Einat and Belmaker 2001) and in controlled studies in patients (Levine 1997). Recently, Einat et al (1998) studied epi-inositol in the elevated plus maze model of rat anxiety and surprisingly found it much more active than myo-inositol.