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/2μl saline) intrastriatal bilaterally on 0day. Sertraline and venlafaxine (10 and 20mg/kg, po) each were administered for 21days 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-α, IL-1β 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-α, IL-6 and IL-1β), 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.


CONCLUSIONS
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.
Neuropharmacology Division, Department of Pharmacology, I.S.F College of Pharmacy, Moga, Punjab, India.
Jaskamal Singh
JS
Gill
Neuropharmacology Division, Department of Pharmacology, I.S.F College of Pharmacy, Moga, Punjab, India; Research Scholar, I. K. Gujral Punjab Technical University, Jalandhar, India.
Sumit
S
Jamwal
Neuropharmacology Division, Department of Pharmacology, I.S.F College of Pharmacy, Moga, Punjab, India. Electronic address: punnubansal79@gmail.com.
Puneet
P
Kumar
Neuropharmacology Division, Department of Pharmacology, I.S.F College of Pharmacy, Moga, Punjab, India. Electronic address: login2rd@gmail.com.
Rahul
R
Deshmukh
D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D018698:Glutamic Acid / Q000378:metabolism; D006816:Huntington Disease / Q000139:chemically induced* / Q000188:drug therapy* / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology; D018377:Neurotransmitter Agents / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D017378:Quinolinic Acid / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D045442:Rotarod Performance Test / Q000379:methods; D020280:Sertraline / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D000069470:Venlafaxine Hydrochloride / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D053583:Interleukin-1beta; D015850:Interleukin-6; D018696:Neuroprotective Agents; D018377:Neurotransmitter Agents; D014409:Tumor Necrosis Factor-alpha; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D000069470:Venlafaxine Hydrochloride; D017378:Quinolinic Acid; D020280:Sertraline
Antidepressants; Huntington’s disease; Neurochemical; Oxidative stress; Quinolinic acid