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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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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DOI: https://doi.org/10.1007/s11011-012-9345-3