DATA PAPERSParkinson's disease-like syndrome in rats induced by 2,9-dimethyl-β-carbolinium ion, a β-carboline occurring in the human brainLorenc-Koci, Elżbietaa; Rommelspacher, Hansc; Schulze, Gertc; Wernicke, Catrinc; Kuter, Katarzynaa; Śmiałowska, Mariab; Wierońska, Joanab; Zięba, Barbarab; Ossowska, KrystynaaAuthor Information Departments of aNeuropsychopharmacology bNeurobiology, Institute of Pharmacology, Polish Academy of Science, Krako´w, Poland cSection of Clinical Neurobiology, Department of Psychiatry, CBF, Charité-University Medicine Berlin, Berlin, Germany Correspondence and requests for reprints to Dr Hans Rommelspacher, MD, Section of Clinical Neurobiology Department of Psychiatry, CBF, Charité-University Medicine Berlin, Eschenallee 3, Berlin 14050, Germany E-mail: [email protected] Sponsorship: This work is supported by the German Bundesministerium für Bildung und Forschung, Grant no. 01 GZ0309 and by the Polish Ministry of Education and Science Grant no. PBZ-MIN-001/P05/18. Received 13 April 2006 Accepted 19 May 2006 Behavioural Pharmacology: September 2006 - Volume 17 - Issue 5-6 - p 463-473 Buy Abstract Regarding the pathogenesis of Parkinson's disease, a neurotoxin hypothesis was proposed following the discovery that 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) produces a Parkinson-like syndrome in humans and primates. Since then, researchers have searched for endogenous and exogenous compounds that are structurally similar to this neurotoxin. Such compounds include β-carbolines, formed from tryptophan and its derivatives. β-carbolines are present naturally in the human brain and cerebrospinal fluid. The present study examined the effect of bilateral, intranigral administration of 2,9-dimethyl-β-carbolinium ion on muscle tone, electromyographic activity, dopamine metabolism in the striatum, and the number of tyrosine hydroxylase-immunoreactive neurons and volume of the substantia nigra in rats. We found that the β-carbolinium ion (15 or 40 nmol per side) caused a significant decrease in the striatal levels of dopamine and its metabolites, which was accompanied by an enhancement of muscle tone and electromyographic activity. Stereological counting revealed that the β-carbolinium caused a significant decrease in the total number of tyrosine hydroxylase-immunoreactive neurons and shrinkage of the substantia nigra. The findings suggest that the methylated β-carbolinium ion produces a dose-dependent degeneration of nigrostriatal neurons, leading to deficits in dopaminergic neurotransmission and an increase of muscle resistance and electromyographic activity, a syndrome equivalent to muscle rigidity in Parkinson's disease. © 2006 Lippincott Williams & Wilkins, Inc.