Antidepressant-like or anxiolytic-like actions of topiramate alone or co-administered with intra-lateral septal infusions of neuropeptide Y in male Wistar rats

Abstract

We tested the effects of intra-lateral septal infusions of neuropeptide Y (NPY) combined with systemic injections of topiramate in the DRL-72s paradigm and the elevated plus-maze test in male Wistar rats. Intra-lateral septal infusions of desipramine (5.0 microg/microl; P<0.05) or intra-lateral septal infusions of NPY (3.0 microg/microl, P<0.05; 3.5 microg/microl, P<0.05) or systemic injections of topiramate (20.0mg/kg, P<0.05; 30.0mg/kg, P<0.05) or subthreshold doses of topiramate (10.0mg/kg) combined with intra-lateral septal infusions of subthreshold doses of NPY (2.5 microg/microl; P<0.05) induced a dose-dependent increase in reinforced lever presses and a cohesive rightward shift of the inter-response time distribution in the DRL 72s task. In the elevated plus-maze test, intra-lateral septal infusions of NPY (3.0 microg/microl, P<0.05; 3.5 microg/microl, P<0.05) or midazolam (10.0 microg/microl; P<0.05) or systemic injections of topiramate (20.0mg/kg, P<0.05; 30.0mg/kg, P<0.05) or subthreshold doses of systemic injections of topiramate (10.0mg/kg) combined with intra-lateral septal infusions of subthreshold doses of NPY (2.5 microg/microl; P<0.05) increased the exploration of the open arms without affecting locomotion. In conclusion, intra-septal NPY has anxiolytic effects in the EPM, and antidepressant effects in the DRL 72s test. Similarly, systemic topiramate has anxiolytic effects in the EPM, and antidepressant effects in the DRL 72s test. Finally, a combination of subthreshold doses of NPY and topiramate together also have anxiolytic and antidepressant effects, suggesting a synergistic effect.