Beneficial effect of candesartan and lisinopril against haloperidol-induced tardive dyskinesia in rat.
BACKGROUND
Tardive dyskinesia is a serious motor disorder of the orofacial region, resulting from chronic neuroleptic treatment of schizophrenia. Candesartan (AT1 antagonist) and lisinopril (ACE inhibitor) has been reported to possess antioxidant and neuroprotective effects. The present study is designed to investigate the effect of candesartan and lisinopril on haloperidol-induced orofacial dyskinesia and oxidative damage in rats.


METHODS
Tardive dyskinesia was induced by administering haloperidol (1 mg/kg i.p.) and concomitantly treated with candesartan (3 and 5 mg/kg p.o.) and lisinopril (10 and 15 mg/kg p.o.) for 3 weeks in male Wistar rats. Various behavioral parameters were assessed on days 0, 7, 14 and 21 and biochemical parameters were estimated at day 22.


RESULTS
Chronic administration of haloperidol significantly increased stereotypic behaviors in rats, which were significantly improved by administration of candesartan and lisinopril. Chronic administration of haloperidol significantly increased oxidative stress and neuro-inflammation in the striatum region of the rat's brain. Co-administration of candesartan and lisinopril significantly attenuated the oxidative damage and neuro-inflammation in the haloperidol-treated rat.


CONCLUSIONS
The present study supports the therapeutic use of candesartan and lisinopril in the treatment of typical antipsychotic-induced orofacial dyskinesia and possible antioxidant and neuro-inflammatory mechanisms.
Department of Pharmacology, Indo-Soviet Friendship College of Pharmacy, India.
Kuldeep Singh
KS
Thakur
Department of Pharmacology, Indo-Soviet Friendship College of Pharmacy, India atishprakash@gmail.com.
Atish
A
Prakash
Department of Pharmacology, Indo-Soviet Friendship College of Pharmacy, India.
Rohit
R
Bisht
Department of Pharmacology, Indo-Soviet Friendship College of Pharmacy, India.
Puneet Kumar
PK
Bansal
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001562:Benzimidazoles / Q000627:therapeutic use*; D001713:Biphenyl Compounds; D001835:Body Weight / Q000187:drug effects; D006120:Grooming; D006220:Haloperidol / Q000009:adverse effects*; D018737:Hand Strength; D053583:Interleukin-1beta / Q000378:metabolism; D017706:Lisinopril / Q000627:therapeutic use*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008409:Mastication; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D009069:Movement Disorders / Q000188:drug therapy* / Q000503:physiopathology; D009573:Nitrites / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D017208:Rats, Wistar; D045442:Rotarod Performance Test; D013239:Stereotyped Behavior; D013777:Tetrazoles / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000975:Antioxidants; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D053583:Interleukin-1beta; D009573:Nitrites; D013777:Tetrazoles; D014409:Tumor Necrosis Factor-alpha; D008315:Malondialdehyde; D017706:Lisinopril; D006220:Haloperidol; C081643:candesartan
Haloperidol; candesartan; lisinopril; oxidative damage; tardive dyskinesia