title: Prevention of haloperidol-induced alterations in brain acetylcholinesterase activity by vitamins B co-administration in a rodent model of tardive dyskinesia.
abstract: Tardive dyskinesia (TD) is an iatrogenic syndrome being a significant adverse outcome of typical and atypical antipsychotic therapy. Recently we demonstrated that vitamins B (B1, B6, B12 alone or in combination) were able to prevent haloperidol-induced orofacial dyskinesia (OD) possibly by their antioxidant activity in the striatum, using a well-established model of TD. Here, based on the fact that alterations in cholinergic neurotransmission are related to TD pathophysiology and that vitamins B seems to influence brain cholinergic neurotransmission, we decided to investigate the effects of vitamins B1, B6, B12 and their association, vitamin B cocktail in haloperidol-induced cholinergic alterations, evaluated by alterations in acetylcholinesterase (AChE) activity, in striatum, prefrontal cortex and hippocampus, as a way to determine the participation of cholinergic neurotransmission, in these vitamins antidyskinetic mechanism. Haloperidol 1 mg/kg i.p. daily administration during 21 days to Wistar rats caused OD while decreased AChE activity in all brain areas studied. Vitamins B administration (B1:B6:B12 at 60:60:0.6 mg/kg, s.c) alone and vitamin B cocktail co-administered with haloperidol prevented OD development and increased AChE activity in all brain areas studied, with the maximum activity increment observed in the hippocampus of the animals co-treated with vitamin B12 and vitamin B cocktail. The antidyskinetic drug, clozapine did not induce OD and increased AChE activity similarly to the groups coadministered with vitamin B and HAL. The present data suggest that vitamins B can prevent haloperidol-induced alterations in AChE activity what can be related to the mechanism underlying their antidyskinetic effect.
authors.affiliation: Department of Physiology and Pharmacology, Federal University of Ceará, Rua Cel. Nunes de Melo 1127, Fortaleza, Ceará, Brazil.
authors.forename: Gersilene Valente
authors.initials: GV
authors.lastname: de Oliveira
authors.forename: Patrícia Xavier Lima
authors.initials: PX
authors.lastname: Gomes
authors.forename: Fernanda Yvelize Ramos
authors.initials: FY
authors.lastname: de Araújo
authors.forename: Silvânia Maria Mendes
authors.initials: SM
authors.lastname: Vasconcelos
authors.forename: Hélio Vitoriano Nobre
authors.initials: HV
authors.lastname: Júnior
authors.forename: Francisca Cléa Florenço
authors.initials: FC
authors.lastname: de Sousa
authors.forename: David F
authors.initials: DF
authors.lastname: de Lucena
authors.forename: Thomas N
authors.initials: TN
authors.lastname: Hyphantis
authors.forename: André Férrer
authors.initials: AF
authors.lastname: Carvalho
authors.forename: Danielle Silveira
authors.initials: DS
authors.lastname: Macêdo
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism*; D000818:Animals; D014150:Antipsychotic Agents / Q000633:toxicity*; D001921:Brain / Q000201:enzymology*; D006220:Haloperidol / Q000633:toxicity*; D008297:Male; D009069:Movement Disorders / Q000201:enzymology / Q000517:prevention & control*; D051381:Rats; D017208:Rats, Wistar; D014803:Vitamin B Complex / Q000627:therapeutic use*
chemical_list: D014150:Antipsychotic Agents; D014803:Vitamin B Complex; D000110:Acetylcholinesterase; D006220:Haloperidol