Pharmacol Biochem Behav. 2007 Oct 25;

Protective effect of Curcumin, the active principle of turmeric
(Curcuma longa) in haloperidol-induced orofacial dyskinesia and
associated behavioural, biochemical and neurochemical changes in rat
brain.

[My paper] Mahendra Bishnoi, Kanwaljit Chopra, Shrinivas K Kulkarni
Tardive dyskinesia (TD) is a motor disorder of the orofacial region
resulting from chronic neuroleptic treatment.
A high incidence and irreversibility of this hyperkinetic disorder has
been considered a major clinical issue in the treatment of
schizophrenia.
The molecular mechanism related to the pathophysiology of tardive
dyskinesia is not completely known.
Various animal studies have demonstrated an enhanced oxidative stress
and increased glutamatergic transmission as well as inhibition in the
glutamate uptake after the chronic administration of haloperidol.
The present study investigated the effect of curcumin, an antioxidant,
in haloperidol-induced tardive dyskinesia by using different
behavioural (orofacial dyskinetic movements, stereotypy, locomotor
activity, % retention), biochemical (lipid peroxidation, reduced
glutathione levels, antioxidant enzyme levels (SOD and catalase) and
neurochemical (neurotransmitter levels) parameters.
Chronic administration of haloperidol (1 mg/kg i.p. for 21 days)
significantly increased vacuous chewing movements (VCM's), tongue
protrusions, facial jerking in rats which was dose-dependently
inhibited by curcumin.
Chronic administration of haloperidol also resulted in increased
dopamine receptor sensitivity as evident by increased locomotor
activity and stereotypy and also decreased % retention time on
elevated plus maze paradigm.
Pretreatment with curcumin reversed these behavioral changes.
Besides, haloperidol also induced oxidative damage in all major
regions of brain which was attenuated by curcumin, especially in the
subcortical region containing striatum.
On chronic administration of haloperidol, there was a decrease in
turnover of dopamine, serotonin and norepinephrine in both cortical
and subcortical regions which was again dose-dependently reversed by
treatment with curcumin.
The findings of the present study suggested for the involvement of
free radicals in the development of neuroleptic-induced tardive
dyskinesia and point to curcumin as a possible therapeutic option to
treat this hyperkinetic movement disorder.

Isr J Med Sci 1993 Sep;29(9):587-92

Iron modulates neuroleptic-induced effects related to the
dopaminergic
system.

Ben-Shachar D, Livne E, Spanier I, Zuk R, Youdim MB
Department of Pharmacology, B. Rappaport Faculty of Medicine,
Technion
Haifa,
Israel.

Long-term neuroleptic medication to schizophrenic patients is often
associated
with extrapyramidal side effects, of which tardive dyskinesia is the
most
severe. The mechanism by which neuroleptics induce these side effects
is
unclear. The dopaminergic system is the main target with which the
neuroleptics
interact in the brain. Intact dopaminergic function is dependent on
normal
iron
metabolism. Thus, the relationship between iron and the neuroleptics
may
elucidate some new aspects of their mechanism of action. Indeed,
peripheral
iron status plays a crucial role in neuroleptic-induced dopamine
supersensitivity. Moreover, neuroleptics such as haloperidol and
chlorpromazine, alter the blood brain barrier (BBB) of the rat and
enhance
the
normally restricted iron transport into the brain. Increased brain
iron
levels
may be related to the toxic effects of these drugs since clozapine,
an
atypical
neuroleptic with a low incidence of extrapyramidal side effects,
prohibits
iron
uptake into the brain but causes sedimentation of iron in brain blood
vessels.
The demonstration that peripheral iron concentrations affect
neuroleptic-induced dopamine receptor supersensitivity as well as
iron
transport into the brain may have therapeutic significance. In
addition, the
different potentials of typical and atypical neuroleptics to increase
iron
transport into the brain may be related to the severity of the side
effects
they induce and to the pathophysiology of tardive dyskinesia.

Publication Types:

Review
Review, tutorial

Quercetin .. an iron binder has been shown to have significant
results /
reduction of incidence of tardive in the animal model ..

Neuropharmacology. 2003 Jun;44(8):1100-6.  Related Articles, Links
Quercetin, a bioflavonoid, attenuates haloperidol-induced orofacial
dyskinesia.
Naidu PS, Singh A, Kulkarni SK.
Pharmacology Division, University Institute of Pharmaceutical
Sciences, Panjab
University, -160014, Chandigarh, India.

Chronic treatment with neuroleptics leads to the development of
abnormal
orofacial movements described as vacuous chewing movements (VCMs) in
rats.
Vacuous chewing movements in rodents are widely accepted as one of the
animal
models of tardive dyskinesia. Oxidative stress and the products of
lipid
peroxidation are implicated in the pathophysiology of various
neurological
disorders including tardive dyskinesia. In the present study chronic
haloperidol (1.0 mg kg(-1) for 21 days) treatment induced vacuous
chewing
movements and tongue protrusions in rats. Co-administration of
quercetin, a
bioflavonoid, dose dependently (25-100 mg kg(-1)) reduced haloperidol-
induced
vacuous chewing movements and tongue protrusions. Biochemical analysis
revealed
that chronic haloperidol treatment induces lipid peroxidation and
decreases the
glutathione (GSH) levels in the forebrains of rats. The antioxidant
defense
enzymes, superoxide dismutase (SOD) and catalase were also decreased
due to
chronic haloperidol treatment. Co-administration of quercetin (25-100
mg
kg(-1)) significantly reduced the lipid peroxidation and restored the
decreased
glutathione levels in these animals. Further quercetin (50-100 mg
kg(-1)) also
reversed the haloperidol-induced decrease in forebrain SOD and
catalase levels
in rats. The major findings of the present study suggested that
oxidative
stress plays a significant role in neuroleptic-induced orofacial
dyskinesia and
quercetin co-administration reverses these behavioral and biochemical
changes.
Quercetin, a naturally occurring bioflavonoid could prove to be a
useful agent
in neuroleptic-induced orofacial dyskinesia.
PMID: 12763102 [PubMed - indexed for MEDLINE]

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