Exploring the ameliorative role of α7 neuronal nicotinic acetylcholine receptor modulation in epilepsy and associated comorbidities in post-PTZ-kindled mice

Aim: The present study aimed to explore the ameliorative role of alpha7 (alpha 7) neuronal nicotinic acetylcholine receptor (nAChR) modulation in epilepsy and associated comorbidities in postpentylenetetrazole (PTZ)-kindled mice. Material and methods: The subconvulsive dose of PTZ (35 mg/kg, i.p.) was used to induce kindling-associated epileptogenesis in mice. After successful kindling, animals were treated intraperitoneally with saline, phenytoin (35 mg/kg), valproate (300 mg/kg), choline chloride (alpha 7 agonist; 400 mg/kg and 800 mg/kg), and methyllycaconitine citrate (alpha 7 antagonist; 3.5 mg/kg and 7.0 mg/kg) for 10 days. All the groups except naive were exposed to PTZ injections on day 3, 6, and 9 of treatment to assess seizure severity score. Epilepsy-associated comorbid depression was evaluated by tail suspension test, sucrose preference test, and plasma corticosterone levels, whereas epilepsy-associated memory deficit condition was assessed by step-through paradigm, Morris water maze, and nitrite levels. Neurochemical perturbations related to epilepsy and associated depression and memory deficit were measured by high-performance liquid chromatography (HPLC). Results: Post-PTZ-kindled mice displayed significant depressive behavior and memory impairment as compared with naive mice as evidenced by corresponding behavioral and biochemical observations. Methyllycaconitine citrate treatment was unable to produce any ameliorative effect in diseased condition. Choline administration dose dependently ameliorated depression, memory impairment, and seizure severity in post-PTZ-kindled mice. The behavioral findings of the study were concurred with neurochemical and biochemical findings. Conclusion: In conclusion, the present study demonstrated the amelioration of epilepsy, comorbid depression, and memory deficit by alpha 7 nAChR agonist choline chloride in PTL-kindled mice model. (C) 2019 Elsevier Inc. All rights reserved.