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-72 s paradigm and the elevated plus-maze test in male Wistar rats. Intra-lateral septal infusions of desipramine (5.0 μg/μl; P < 0.05) or intra-lateral septal infusions of NPY (3.0 μg/μl, P < 0.05; 3.5 μg/μl, P < 0.05) or systemic injections of topiramate (20.0 mg/kg, P < 0.05; 30.0 mg/kg, P < 0.05) or subthreshold doses of topiramate (10.0 mg/kg) combined with intra-lateral septal infusions of subthreshold doses of NPY (2.5 μg/μl; 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 72 s task. In the elevated plus-maze test, intra-lateral septal infusions of NPY (3.0 μg/μl, P < 0.05; 3.5 μg/μl, P < 0.05) or midazolam (10.0 μg/μl; P < 0.05) or systemic injections of topiramate (20.0 mg/kg, P < 0.05; 30.0 mg/kg, P < 0.05) or subthreshold doses of systemic injections of topiramate (10.0 mg/kg) combined with intra-lateral septal infusions of subthreshold doses of NPY (2.5 μg/μl; 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 72 s test. Similarly, systemic topiramate has anxiolytic effects in the EPM, and antidepressant effects in the DRL 72 s test. Finally, a combination of subthreshold doses of NPY and topiramate together also have anxiolytic and antidepressant effects, suggesting a synergistic effect.