Chronic haloperidol treatment leads to an increase in the intramembrane interaction between adenosine A2 and dopamine D2 receptors in the neostriatum.
Stimulation of adenosine A2 receptors (with the selective adenosine A2 agonist CGS 21680) in rat striatal membrane preparations, produces a decrease in both the affinity of D2 receptors and the transduction of the signal from the D2 receptor to the G protein. This intramembrane A2-D2 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 A2-D2 interaction, which may underlie the observed higher sensitivity to the behavioural effects induced by adenosine antagonists found in these animals. 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 A2-D2 interaction in the neostriatum and with a higher sensitivity to the behavioural effects induced by adenosine antagonists.(ABSTRACT TRUNCATED AT 250 WORDS)
Ferré
S
S
Department of Neurochemistry, C.S.I.C., Barcelona, Spain.
Schwarcz
R
R
Li
X M
XM
Snaprud
P
P
Ogren
S O
SO
Fuxe
K
K
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001667:Binding, Competitive / Q000187:drug effects; D065127:Dopamine D2 Receptor Antagonists; D006220:Haloperidol / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D009043:Motor Activity / Q000187:drug effects; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism*; D010627:Phenethylamines / Q000494:pharmacology; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D020891:Raclopride; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000187:drug effects*; D018047:Receptors, Purinergic P1 / Q000187:drug effects*; D012457:Salicylamides / Q000494:pharmacology; D013806:Theophylline / Q000494:pharmacology
D000959:Antihypertensive Agents; D065127:Dopamine D2 Receptor Antagonists; D010627:Phenethylamines; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D017448:Receptors, Dopamine D2; D018047:Receptors, Purinergic P1; D012457:Salicylamides; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; D020891:Raclopride; D013806:Theophylline; D006220:Haloperidol; D000241:Adenosine