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Prevention of haloperidol-induced alterations in brain acetylcholinesterase activity by vitamins B co-administration in a rodent model of tardive dyskinesia

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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.

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Abbreviations

ACh:

Acetylcholine

AChE:

Acetylcholinesterase

ChIs:

Cholinergic interneurons

DA:

Dopamine

HC:

Hippocampus

OD:

Orofacial dyskinesia

PFC:

Prefrontal cortex

ST:

Striatum

TD:

Tardive dyskinesia

TP:

Tongue protrusion

VCM:

Vacuous chewing movements

Vitamin B1:

Thiamine

Vitamin B6:

Pyridoxine

Vitamin B12:

Cyanocobalamin

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Authors and Affiliations

  1. Department of Physiology and Pharmacology, Federal University of Ceará, Rua Cel. Nunes de Melo 1127, Fortaleza, 60431-270, Ceará, Brazil

    Gersilene Valente de Oliveira, Patrícia Xavier Lima Gomes, Fernanda Yvelize Ramos de Araújo, Silvânia Maria Mendes Vasconcelos, Francisca Cléa Florenço de Sousa, David F. de Lucena & Danielle Silveira Macêdo

  2. Department of Pharmacy, Federal University of Ceará, Fortaleza, Ceará, Brazil

    Hélio Vitoriano Nobre Júnior

  3. Department of Psychiatry, School of Medicine, University of Ioannina, Ioaninna, Greece

    Thomas N. Hyphantis

  4. Department of Clinical Medicine, Federal University of Ceará, Fortaleza, Ceará, Brazil

    André Férrer Carvalho

Authors
  1. Gersilene Valente de Oliveira
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  2. Patrícia Xavier Lima Gomes
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  3. Fernanda Yvelize Ramos de Araújo
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  4. Silvânia Maria Mendes Vasconcelos
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  5. Hélio Vitoriano Nobre Júnior
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  6. Francisca Cléa Florenço de Sousa
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  7. David F. de Lucena
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  8. Thomas N. Hyphantis
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  9. André Férrer Carvalho
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  10. Danielle Silveira Macêdo
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Correspondence to Danielle Silveira Macêdo.

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de Oliveira, G.V., Gomes, P.X.L., de Araújo, F.Y.R. et al. Prevention of haloperidol-induced alterations in brain acetylcholinesterase activity by vitamins B co-administration in a rodent model of tardive dyskinesia. Metab Brain Dis 28, 53–59 (2013). https://doi.org/10.1007/s11011-012-9345-3

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