Effects of sigma ligands on NMDA receptor function in the bulbectomy model of depression: a behavioural study in the rat.

Sigma (sigma) ligands have been shown to modulate NMDA receptor activity. In the present study we used the olfactory bulbectomy (OBX) animal model of depression to assess the effects of the sigma1 ligand igmesine on OBX-induced behaviour. Behavioural experiments demonstrated OBX (saline-treated) rats to have increased dizocilpine-induced behavioural modifications, including locomotor and circling activity as compared to Sham rats (saline-treated). A short-term (7 d) treatment with low doses of igmesine (50-200 microg/kg.d s.c.) had no effect on dizocilpine-induced behaviour while long-term treatments (14 d) with low doses of igmesine reversed the effect of the bulbectomy such that the treated OBX rats' behaviour was not significantly different from Sham-saline rats. Short-term treatments with high doses of igmesine (500-1000 microg/kg.d) also reversed the increased locomotor and circling behaviour seen in OBX rats (saline-treated) while long-term treatments with the same high doses did not. These results provide behavioural evidence for sigma ligand's potential to reverse some OBX-induced behaviours. Moreover, they support the notion of a bell-shaped dose-response curve previously reported for sigma ligands.