title: Lipoic acid and haloperidol-induced vacuous chewing movements: Implications for prophylactic antioxidant use in tardive dyskinesia.
abstract: Tardive dyskinesia (TD), a potentially irreversible antipsychotic (AP)-related movement disorder, is a risk with all currently available antipsychotics. AP-induced vacuous chewing movements (VCMs) in rats, a preclinical model of TD, can be attenuated by antioxidant-based treatments although there is a shortage of well-designed studies. Lipoic acid (LA) represents a candidate antioxidant for the treatment of oxidative stress-related nervous system disorders; accordingly, its effects on AP-induced VCMs and striatal oxidative stress were examined. Rats treated with haloperidol decanoate (HAL; 21mg/kg every 3weeks, IM) for 12weeks were concurrently treated with LA (10 or 20mg/kg, PO). VCMs were assessed weekly by a blinded rater, and locomotor activity was evaluated as were striatal lipid peroxidation markers and serum HAL levels. VCMs were decreased by the lower dose (nonsignificant), whereas a significant increase was recorded with the higher dose of LA. HAL decreased locomotor activity and this was unaffected by LA. Striatal malondialdehyde (MDA) levels in HAL-treated rats were reduced by both LA doses, while 4-hydroxynonenal (4-HNE) levels were predictive of final VCM scores (averaged across weeks 10-12). Study limitations include differences between antipsychotics in terms of oxidative stress, LA dosing, choice of biomarkers for lipid peroxidation, and generalizability to TD in humans. Collectively, current preclinical evidence does not support a "protective" role for antioxidants in preventing TD or its progression, although clinical evidence offers limited evidence supporting such an approach.
authors: Centre for Addiction and Mental Health, Toronto, ON, Canada; Institute of Medical Science, University of Toronto, Toronto, ON, Canada.
authors: Joshua
authors: J
authors: Lister
authors: Centre for Addiction and Mental Health, Toronto, ON, Canada; Institute of Medical Science, University of Toronto, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada; Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada.
authors: Ana C
authors: AC
authors: Andreazza
authors: Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada.
authors: Bushra
authors: B
authors: Navaid
authors: Centre for Addiction and Mental Health, Toronto, ON, Canada.
authors: Virginia S
authors: VS
authors: Wilson
authors: Centre for Addiction and Mental Health, Toronto, ON, Canada.
authors: Celine
authors: C
authors: Teo
authors: Centre for Addiction and Mental Health, Toronto, ON, Canada.
authors: Yasika
authors: Y
authors: Nesarajah
authors: Centre for Addiction and Mental Health, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
authors: Alan A
authors: AA
authors: Wilson
authors: Centre for Addiction and Mental Health, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada; Department of Psychology, University of Toronto, Toronto, ON, Canada; Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada.
authors: José N
authors: JN
authors: Nobrega
authors: Centre for Addiction and Mental Health, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada; Department of Psychology, University of Toronto, Toronto, ON, Canada.
authors: Paul J
authors: PJ
authors: Fletcher
authors: Centre for Addiction and Mental Health, Toronto, ON, Canada; Institute of Medical Science, University of Toronto, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada. Electronic address: gary.remington@camh.ca.
authors: Gary
authors: G
authors: Remington
mesh_terms: D000447:Aldehydes / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D014150:Antipsychotic Agents / Q000097:blood / Q000633:toxicity*; D006220:Haloperidol / Q000097:blood / Q000633:toxicity*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008409:Mastication / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000071057:Tardive Dyskinesia / Q000139:chemically induced* / Q000517:prevention & control*; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D008063:Thioctic Acid / Q000627:therapeutic use* / Q000633:toxicity
chemical_list: D000447:Aldehydes; D000975:Antioxidants; D014150:Antipsychotic Agents; D017392:Thiobarbituric Acid Reactive Substances; D008315:Malondialdehyde; D008063:Thioctic Acid; D006220:Haloperidol; C027576:4-hydroxy-2-nonenal
keywords: Animal models; Antipsychotics; Psychopharmacology; Tardive dyskinesia