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Titolo:
CHRONIC HALOPERIDOL TREATMENT LEADS TO AN INCREASE IN THE INTRAMEMBRANE INTERACTION BETWEEN ADENOSINE A(2) AND DOPAMINE D-2 RECEPTORS IN THE NEOSTRIATUM
Autore:
FERRE S; SCHWARCZ R; LI XM; SNAPRUD P; OGREN SO; FUXE K;
Indirizzi:
CSIC,DEPT NEUROCHEM,JORDI GIRONA 18-26 E-08034 BARCELONA SPAIN MARYLAND PSYCHIAT RES CTR BALTIMORE MD 21228 KAROLINSKA INST,DEPT HISTOL & NEUROBIOL S-10401 STOCKHOLM SWEDEN
Titolo Testata:
Psychopharmacology
fascicolo: 3, volume: 116, anno: 1994,
pagine: 279 - 284
Fonte:
ISI
Lingua:
ENG
Soggetto:
CENTRAL-NERVOUS-SYSTEM; MOLECULAR-CLONING; RAT-BRAIN; HIGH-AFFINITY; CGS 21680; BINDING; AGONIST; STRIATUM; SUPERSENSITIVITY; A2-RECEPTORS;
Keywords:
ADENOSINE A(2) RECEPTOR; DOPAMINE D-2 RECEPTOR; METHYLXANTHINE; TARDIVE DYSKINESIAS; RECEPTOR-RECEPTOR INTERACTION; RAT;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
44
Recensione:
Indirizzi per estratti:
Citazione:
S. Ferre et al., "CHRONIC HALOPERIDOL TREATMENT LEADS TO AN INCREASE IN THE INTRAMEMBRANE INTERACTION BETWEEN ADENOSINE A(2) AND DOPAMINE D-2 RECEPTORS IN THE NEOSTRIATUM", Psychopharmacology, 116(3), 1994, pp. 279-284

Abstract

Stimulation of adenosine A(2) receptors (with the selective adenosineA(2) agonist CGS 21680) in rat striatal membrane preparations, produces a decrease in both the affinity of D-2 receptors and the transduction of the signal from the D-2 receptor to the G protein. This intramembrane A(2)-D-2 interaction might be responsible for the behavioural depressant effects of adenosine agonists and for the behavioural stimulant effects of adenosine antagonists such as caffeine and theophylline. Dopamine denervation induces an increase in the intramembrane A(2)-D-2 interaction, which may underlie the observed higher sensitivity to the behavioural effects induced by adenosine antagonists found in theseanimals. The present study was designed to examine if chronic treatment with haloperidol, which also produces dopamine receptor supersensitivity, is also associated with an increase in the intramembrane A(2)-D-2 interaction in the neostriatum and with a higher sensitivity to thebehavioural effects induced by adenosine antagonists. The data showedthat: (i) haloperidol pretreatment causes a higher binding of the D-2antagonist [H-3] raclopride in striatal membrane preparations due to an increase in the number of D-2 receptors without changes in their affinity for the antagonist (increase in B-max without changes in k(d));(ii) GCS 21680 decreases the affinity of dopamine for the D-2 receptor, by increasing the equilibrium dissociation constants of high (K-h) and low affinity (K-l) dopamine D-2 binding sites and increases the proportion of high affinity binding sites (R(h)); (iii) a low dose of CGS 21680 (3 nM), which is ineffective in membrane preparations from neostriatum of nontreated animals, is effective in membranes from the striatum of haloperidol-pretreated animals; (iv)the nonselective adenosine antagonist theophylline (20 mg/kg SC) causes a higher motor activation in rats pretreated with haloperidol. The possible relevance of these results for the pathophysiology and treatment of tardive dyskinesiasis discussed.

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Documento generato il 18/09/20 alle ore 17:09:21