Sertraline and venlafaxine improves motor performance and neurobehavioral deficit in quinolinic acid induced Huntington's like symptoms in rats: Possible neurotransmitters modulation

Background: Huntington Disease is autosomal, fatal and progressive neurodegenerative disorder for which clinically available drugs offer only symptomatic relief. Emerging strides have indicated that antidepressants improve motor performance, restore neurotransmitters level, ameliorates striatal atrophy, increases BDNF level and may enhance neurogenesis. Therefore, we investigated sertraline and venlafaxine, clinically available drugs for depression with numerous neuroprotective properties, for their beneficial effects, if any, in quinolinic acid induced Huntington's like symptoms in rats. Methods: Rats were administered quinolinic acid (QA) (200 nmol/2 mu l saline) intrastriatal bilaterally on 0 day. Sertraline and venlafaxine (10 and 20 mg/kg, po) each were administered for 21 days once a day. Motor performance was assessed using rotarod test, grip strength test, narrow beam walk test on weekly basis. On day 22, animals were sacrificed and rat striatum was isolated for biochemical (LPO, GSH and Nitrite), neuroinflammation (TNF-alpha, IL-1 beta and IL-6) and neurochemical analysis (GABA, glutamate, norepinephrine, dopamine, serotonin, DOPAC, HVA and 5-HIAA). Results: QA treatment significantly altered body weight, motor performance, oxidative defense (increased LPO, nitrite and decreased GSH), pro-inflammatory cytokines levels (TNF-alpha, IL-6 and IL-1 beta), neurochemical level (GABA, glutamate, nor-epinephrine, dopamine, serotonin, HVA, DOPAC, 5-HIAA). Sertraline and venlafaxine at selected doses significantly attenuated QA induced alterations in striatum. Conclusion: The present study suggests that modulation of monoamines level, normalization of GABA and glutamatergic signaling, anti-oxidant and anti-inflammatory properties could underlie the neuroprotective effect of sertraline and venlafaxine in QA induced Huntington's like symptoms. (C) 2016 Published by Elsevier Sp. z o.o. on behalf of Institute of Pharmacology, Polish Academy of Sciences.