Enhanced striatal dopamine D2 receptor-induced [35S]GTPγS 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-[S-35]thio)triphosphate ([S-35]GTP gamma S) and [H-3]spiperone binding were determined in striatal homogenates. Maximal [H-3]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 [S-35]GTP gamma S 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. (C) 1999 Elsevier Science B.V. All rights reserved.