Enhanced striatal dopamine D(2) receptor-induced [35S]GTPgammaS binding after haloperidol treatment.
Dopamine receptor-G protein coupling and dopamine D(2) receptor density were assessed in rats treated for 3 weeks with either haloperidol (2 mg/kg; i.p.) or vehicle. After 3 days of withdrawal, agonist-induced guanosine 5'-O-(gamma-[35S]thio)triphosphate ([35S]GTPgammaS) and [3H]spiperone binding were determined in striatal homogenates. Maximal [3H]spiperone binding was increased (24.8%, P<0.01) following haloperidol treatment. The efficacy of dopamine and the dopamine D(2) receptor agonist R(-)-10, 11-dihydroxy-N-n-propylnorapomorphine (NPA) to induce [35S]GTPgammaS binding were found to be increased by 24.1% (P<0.01) and 44.6% (P<0. 001), respectively. When measured in the presence of a saturating concentration of a dopamine D(2) receptor antagonist, the response to dopamine was not significantly affected by haloperidol treatment. In addition, the measurement of haloperidol-induced catalepsy confirmed that the efficient dopamine receptor blockade was followed by a progressive development of dopaminergic supersensitivity. Taken together, these results indicate that a functional pool of dopamine D(2) receptors is increased after prolonged haloperidol administration.
Geurts
M
M
Laboratoire de pharmacologie, U.C.L. 54.10, Université catholique de Louvain, Avenue Hippocrate 54, B-1200, Brussels, Belgium.
Hermans
E
E
Maloteaux
J M
JM
D000818:Animals; D001058:Apomorphine / Q000031:analogs & derivatives / Q000494:pharmacology; D001667:Binding, Competitive / Q000187:drug effects; D002375:Catalepsy / Q000139:chemically induced / Q000503:physiopathology; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000009:adverse effects / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism*; D006220:Haloperidol / Q000009:adverse effects / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D013134:Spiperone / Q000378:metabolism; D013462:Sulfur Radioisotopes; D014316:Tritium; D015854:Up-Regulation
D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D017448:Receptors, Dopamine D2; D013462:Sulfur Radioisotopes; D014316:Tritium; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D013134:Spiperone; C009074:N-n-propylnorapomorphine; D006220:Haloperidol; D001058:Apomorphine; D004298:Dopamine