Abstract
The adenosine A2A receptor antagonist SCH 58261 increases the turning behaviour induced by L-dopa in unilaterally 6-hydroxydopamine (6-OHDA)-lesioned rats. In this study we have evaluated the effect of a chronic intermittent administration of L-dopa or SCH 58261 plus L-dopa on turning behaviour. Chronic intermittent administration of SCH 58261 plus L-dopa produced a stable turning behaviour during the course of the treatment, whereas L-dopa alone produced a progressive increase in turning behaviour. Moreover, repeated administration of SCH 58261 failed to produce tolerance to its ability to potentiate L-dopa-induced turning behaviour. The results indicate that SCH 58261 is effective after chronic administration and suggest that SCH 58261 plus L-dopa, differently from Ldopa alone, does not produce alterations in motor responses during the course of the treatment.
MeSH terms
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Animals
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Antiparkinson Agents / pharmacology*
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Denervation
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Dopamine / metabolism*
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Dose-Response Relationship, Drug
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Drug Administration Schedule
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Drug Interactions / physiology
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Drug Therapy, Combination
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Drug Tolerance / physiology
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Levodopa / pharmacology*
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Male
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Motor Activity / drug effects
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Motor Activity / physiology
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Neostriatum / drug effects
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Neostriatum / metabolism
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Neostriatum / physiopathology
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Neural Pathways / drug effects
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Neural Pathways / metabolism
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Neural Pathways / physiopathology
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Neuroprotective Agents / pharmacology*
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Oxidopamine / pharmacology
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Parkinsonian Disorders / drug therapy*
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Parkinsonian Disorders / metabolism
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Parkinsonian Disorders / physiopathology
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Purinergic P1 Receptor Antagonists
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Pyrimidines / pharmacology*
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Rats
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Rats, Sprague-Dawley
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Receptor, Adenosine A2A
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Receptors, Purinergic P1 / metabolism*
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Substantia Nigra / drug effects
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Substantia Nigra / metabolism
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Substantia Nigra / physiopathology
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Sympatholytics / pharmacology
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Triazoles / pharmacology*
Substances
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5-amino-7-(2-phenylethyl)-2-(2-furyl)pyrazolo(4,3-e)-1,2,4-triazolo(1,5-c)pyrimidine
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Antiparkinson Agents
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Neuroprotective Agents
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Purinergic P1 Receptor Antagonists
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Pyrimidines
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Receptor, Adenosine A2A
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Receptors, Purinergic P1
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Sympatholytics
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Triazoles
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Levodopa
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Oxidopamine
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Dopamine