Treatment with 1,2,3,4,-tetrahydroisoquinoline affects glutamate release in the striatum but not the binding of [3H]MK-801 to NMDA receptors in the dopaminergic structures of the rat brain.
Overactivity of the glutamatergic system is thought to be closely related to the pathogenesis of Parkinson's disease. This study aimed to examine the effect of acute administration of 1,2,3,4-tetrahydroisoquinoline (TIQ), an endo- and exogenous amine suspected of inducing parkinsonism in humans on the release of glutamate in the striatum as well as to assess the impact of its chronic treatment on the binding of [(3)H]MK-801 to NMDA receptors in the dopaminergic structures of the rat brain. Striatal release of glutamate was measured in conscious, freely moving rats using a microdialysis method. [(3)H]MK-801 binding to NMDA receptors was examined in the striatum, nucleus accumbens and prefrontal cortex by autoradiographic method. TIQ administered acutely at a single dose of 100 mg/kg significantly decreased the level of extracellular glutamate, with the concentration decrease starting at 60 min and reaching minimum at 210 min after TIQ injection. TIQ administered chronically at the same dose for 3 weeks did not alter the binding of [(3)H]MK-801 to NMDA receptors in the examined dopaminergic structures at either 4 or 72 h after the last chronic injection. These results indicate that TIQ can modulate glutamate release in the striatum but that it does not affect the level of NMDA receptors in that structure. The latter data complete a list of recently published evidence that distinctly suggest that TIQ acts in the mammalian brain rather as a neuromodulator or even as a neuroprotective agent but not as a parkinsonism-inducing neurotoxin.
Lorenc-Koci
Elzbieta
E
Department of Neuro-Psychopharmacology, Institute of Pharmacology, Polish Academy of Sciences, Smetna 12, PL 31-343 Kraków, Poland. lorenc@if-pan.krakow.pl
Gołembiowska
Krystyna
K
Pietraszek
Małgorzata
M
Wardas
Jadwiga
J
D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D016291:Dizocilpine Maleate / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism; D004334:Drug Administration Schedule; D018691:Excitatory Amino Acid Antagonists / Q000378:metabolism; D018698:Glutamic Acid / Q000187:drug effects* / Q000378:metabolism; D017551:Microdialysis; D010300:Parkinson Disease / Q000503:physiopathology; D011485:Protein Binding; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D044005:Tetrahydroisoquinolines / Q000008:administration & dosage / Q000494:pharmacology*; D013997:Time Factors
D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D044005:Tetrahydroisoquinolines; D018698:Glutamic Acid; C014843:1,2,3,4-tetrahydroisoquinoline; D016291:Dizocilpine Maleate; D004298:Dopamine