Attenuation of haloperidol-induced catalepsy by noradrenaline and L-threo-DOPS

W D J Verhagen - Kamerbeek; I Hazemeijer; J Korf; J P W F Lakke

doi:10.1007/BF02252619

Attenuation of haloperidol-induced catalepsy by noradrenaline and L-threo-DOPS

W D J Verhagen - Kamerbeek^*, I Hazemeijer, J Korf, J P W F Lakke

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

10 Citations (Scopus)

Abstract

In addition to impaired dopaminergic neurotransmission a dysfunctional noradrenergic system has been demonstrated in Parkinson's disease. L-threo-3,4-dihydroxyphenylserine (DOPS), a synthetic precursor of noradrenaline (NA), appears to be effective in the treatment of some akinetic symptoms in parkinsonian patients. In the present study the possible effect of DOPS was studied in rats, in which catalepsy was induced with haloperidol as a model for parkinsonian akinesia.

Intravenous infusion of NA (1.5 and 15 mug/kg) or DOPS (2 and 4 mg/kg) in male Wistar rats (240 - 290 g) significantly decreased catalepsy. The effect of DOPS was abolished by pretreatment with the peripheral decarboxylase inhibitor benserazide (2 mg/kg). Pretreatment with Ro 40-7592, a catechol-O-methyltransferase inhibitor, potentiated and prolonged the anticataleptic effect of DOPS.

The findings suggest a peripheral site of NA mediated anticataleptic action. Therapy with DOPS may be successful only without a peripheral decarboxylase inhibitor. Moreover, the therapeutic effect of DOPS may be potentiated by COMT inhibition.

Original language	English
Pages (from-to)	17-26
Number of pages	10
Journal	Journal of neural transmission-Parkinsons disease and dementia section
Volume	6
Issue number	1
DOIs	https://doi.org/10.1007/BF02252619
Publication status	Published - 1993

Keywords

NORADRENALINE
L-THREO-3,4-DIHYDROXYPHENYLSERINE (DOPS)
CATALEPSY
PARKINSONS DISEASE
COMT INHIBITION
RO 40-7592
PARKINSONS-DISEASE
NOREPINEPHRINE PRECURSOR
STRIATAL DOPAMINE
RAT-BRAIN
METABOLISM
L-THREO-3,4-DIHYDROXYPHENYLSERINE
REVERSAL
STRESS

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Attenuation of haloperidol-induced catalepsy by noradrenaline and L-threo-DOPS
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title = "Attenuation of haloperidol-induced catalepsy by noradrenaline and L-threo-DOPS",

abstract = "In addition to impaired dopaminergic neurotransmission a dysfunctional noradrenergic system has been demonstrated in Parkinson's disease. L-threo-3,4-dihydroxyphenylserine (DOPS), a synthetic precursor of noradrenaline (NA), appears to be effective in the treatment of some akinetic symptoms in parkinsonian patients. In the present study the possible effect of DOPS was studied in rats, in which catalepsy was induced with haloperidol as a model for parkinsonian akinesia.Intravenous infusion of NA (1.5 and 15 mug/kg) or DOPS (2 and 4 mg/kg) in male Wistar rats (240 - 290 g) significantly decreased catalepsy. The effect of DOPS was abolished by pretreatment with the peripheral decarboxylase inhibitor benserazide (2 mg/kg). Pretreatment with Ro 40-7592, a catechol-O-methyltransferase inhibitor, potentiated and prolonged the anticataleptic effect of DOPS.The findings suggest a peripheral site of NA mediated anticataleptic action. Therapy with DOPS may be successful only without a peripheral decarboxylase inhibitor. Moreover, the therapeutic effect of DOPS may be potentiated by COMT inhibition.",

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year = "1993",

doi = "10.1007/BF02252619",

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pages = "17--26",

journal = "Journal of neural transmission-Parkinsons disease and dementia section",

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AU - Verhagen - Kamerbeek, W D J

AU - Hazemeijer, I

AU - Korf, J

AU - Lakke, J P W F

PY - 1993

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N2 - In addition to impaired dopaminergic neurotransmission a dysfunctional noradrenergic system has been demonstrated in Parkinson's disease. L-threo-3,4-dihydroxyphenylserine (DOPS), a synthetic precursor of noradrenaline (NA), appears to be effective in the treatment of some akinetic symptoms in parkinsonian patients. In the present study the possible effect of DOPS was studied in rats, in which catalepsy was induced with haloperidol as a model for parkinsonian akinesia.Intravenous infusion of NA (1.5 and 15 mug/kg) or DOPS (2 and 4 mg/kg) in male Wistar rats (240 - 290 g) significantly decreased catalepsy. The effect of DOPS was abolished by pretreatment with the peripheral decarboxylase inhibitor benserazide (2 mg/kg). Pretreatment with Ro 40-7592, a catechol-O-methyltransferase inhibitor, potentiated and prolonged the anticataleptic effect of DOPS.The findings suggest a peripheral site of NA mediated anticataleptic action. Therapy with DOPS may be successful only without a peripheral decarboxylase inhibitor. Moreover, the therapeutic effect of DOPS may be potentiated by COMT inhibition.

AB - In addition to impaired dopaminergic neurotransmission a dysfunctional noradrenergic system has been demonstrated in Parkinson's disease. L-threo-3,4-dihydroxyphenylserine (DOPS), a synthetic precursor of noradrenaline (NA), appears to be effective in the treatment of some akinetic symptoms in parkinsonian patients. In the present study the possible effect of DOPS was studied in rats, in which catalepsy was induced with haloperidol as a model for parkinsonian akinesia.Intravenous infusion of NA (1.5 and 15 mug/kg) or DOPS (2 and 4 mg/kg) in male Wistar rats (240 - 290 g) significantly decreased catalepsy. The effect of DOPS was abolished by pretreatment with the peripheral decarboxylase inhibitor benserazide (2 mg/kg). Pretreatment with Ro 40-7592, a catechol-O-methyltransferase inhibitor, potentiated and prolonged the anticataleptic effect of DOPS.The findings suggest a peripheral site of NA mediated anticataleptic action. Therapy with DOPS may be successful only without a peripheral decarboxylase inhibitor. Moreover, the therapeutic effect of DOPS may be potentiated by COMT inhibition.

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KW - PARKINSONS-DISEASE

KW - NOREPINEPHRINE PRECURSOR

KW - STRIATAL DOPAMINE

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KW - METABOLISM

KW - L-THREO-3,4-DIHYDROXYPHENYLSERINE

KW - REVERSAL

KW - STRESS

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DO - 10.1007/BF02252619

M3 - Article

SN - 0936-3076

VL - 6

SP - 17

EP - 26

JO - Journal of neural transmission-Parkinsons disease and dementia section

JF - Journal of neural transmission-Parkinsons disease and dementia section

IS - 1

ER -

Attenuation of haloperidol-induced catalepsy by noradrenaline and L-threo-DOPS

Abstract

Keywords

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