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

• Published in: Journal of Neural Transmission - Parkinson's Disease and Dementia Section Vol. 6; no. 1; pp. 17 - 26
• Main Authors: VERHAGEN-KAMERBEEK, W. D. J, HAZEMEIJER, I, KORF, J, LAKKE, J. P. W. F
• Format: Journal Article
• Language: English
• Published: Wien Springer 01-01-1993; New York, NY
• Subjects: Animals; Aromatic Amino Acid Decarboxylase Inhibitors; Benserazide - pharmacology; Benzophenones - pharmacology; Biological and medical sciences; Catalepsy - chemically induced; Catalepsy - prevention & control; Catechol O-Methyltransferase Inhibitors; Droxidopa - antagonists & inhibitors; Droxidopa - pharmacology; Drug Interactions; Haloperidol - antagonists & inhibitors; Haloperidol - toxicity; Male; Medical sciences; Nervous system involvement in other diseases. Miscellaneous; Neurology; Nitrophenols; Norepinephrine - pharmacology; Postural Balance - drug effects; Rats; Rats, Wistar; Animal model; Nervous system diseases; Rat; Rodentia; Catalepsy; Parkinson disease; Catecholamine; Precursor; Vertebrata; Mammalia; Noradrenergic transmission; Degenerative disease; Norepinephrine
• ISSN: 0936-3076; 1435-1463
• DOI: 10.1007/BF02252619

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 micrograms/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.