Premium
Catalepsy induced by a blockade of dopamine D 1 or D 2 receptors was reversed by a concomitant blockade of adenosine A 2A receptors in the caudate‐putamen of rats
Author(s) -
Hauber Wolfgang,
Neuscheler Patric,
Nagel Jens,
Müller Christa E.
Publication year - 2001
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1046/j.0953-816x.2001.01759.x
Subject(s) - blockade , catalepsy , pharmacology , chemistry , sch 23390 , receptor antagonist , dopamine receptor d2 , adenosine receptor , receptor , dopamine receptor d3 , medicine , endocrinology , antagonist , dopamine , agonist , haloperidol
The present study sought to determine, in more detail, the effects of an unselective and a selective adenosine A 2A receptor blockade on catalepsy induced by a blockade of dopamine D 1 or D 2 receptors in rats. The results demonstrated that systemic administration of the unselective A 1 /A 2 receptor antagonist, theophylline and the selective A 2A receptor antagonist, CSC potently reversed catalepsy induced by a systemic D 2 receptor blockade with raclopride or by a bilateral blockade of D 2 receptors in the caudate‐putamen (CPu) with S(–)sulpiride. Likewise, systemic administration of theophylline and CSC reversed catalepsy induced by a systemic D 1 receptor blockade with SCH23390; theophylline also counteracted catalepsy after an intra‐CPu D 1 receptor blockade with SCH23390. Intracerebral co‐microinfusions of the selective A 2A receptor antagonist, MSX‐3 together with a D 1 (SCH23390) or D 2 receptor [S(–) sulpiride] antagonist revealed that catalepsy due to intra‐CPu D 1 or D 2 receptor blockade can be potently reversed by an intra‐CPu A 2A receptor blockade. In conclusion, our results with systemic and intra‐CPu drug administration demonstrate that D 1 and D 2 receptor‐mediated catalepsy can both be reversed by a concomitant blockade of A 2A receptors. Our results implicate that the CPu is a critical neural substrate for antagonistic interactions of a D 1/ D 2 receptor blockade and an A 2A receptor blockade in control of motor activity. The present results provide further support for the view that A 2A receptor antagonists may be potential therapeutics for the treatment of Parkinson's disease.