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Neuroleptics up-regulate adenosine A2a receptors in rat striatum: implications for the mechanism and the treatment of tardive dyskinesia.

Abstract：

:Neuroleptics, which are potent dopamine receptor antagonists, are used to treat psychosis. In the striatum, dopamine subtype-2 (D2) receptors interact with high-affinity adenosine subtype-2 (A2a) receptors. To examine the effect of various neuroleptics on the major subtypes of striatal dopamine and adenosine receptors, rats received 28 daily intraperitoneal injections of these drugs. Haloperidol (1.5 mg/kg/day) increased the density of striatal D2 receptors by 24% without changing their affinity for [3H]sulpiride. Haloperidol increased the density of striatal A2a receptors by 33% (control, 522.4 +/- 20.7 fmol/mg of protein; haloperidol, 694.6 +/- 23.6 fmol/mg of protein; p < 0.001) without changing their affinity for [3H]CGS-21680 (control, 19.2 +/- 2.2 nM; haloperidol, 21.4 +/- 2.3 nM). In contrast, haloperidol had no such effect on striatal dopamine subtype-1 (D1) and adenosine subtype-1 (A1) receptors. Binding characteristics and the pharmacological displacement profile of the increased [3H]CGS-21680 binding sites confirmed them as A2a receptors. Comparing different classes of neuroleptics showed that the typical neuroleptics haloperidol and fluphenazine (1.5 mg/kg/day) increased D2 receptor densities, whereas the atypical neuroleptics sulpiride (100 mg/kg/day) and clozapine (20 mg/kg/day) did not (control, 290.3 +/- 8.7 fmol/mg of protein; haloperidol, 358.1 +/- 6.9 fmol/mg of protein; fluphenazine, 381.3 +/- 13.6 fmol/mg of protein; sulpiride, 319.8 +/- 18.9 fmol/mg of protein; clozapine, 309.2 +/- 13.7 fmol/mg of protein).(ABSTRACT TRUNCATED AT 250 WORDS)

journal_name

J Neurochem

journal_title

Journal of neurochemistry

authors

Parsons B,Togasaki DM,Kassir S,Przedborski S

doi

10.1046/j.1471-4159.1995.65052057.x

subject

Has Abstract

pub_date

1995-11-01 00:00:00

pages

2057-64

issue

5

eissn

0022-3042

issn

1471-4159

journal_volume

65

pub_type

杂志文章

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