Chronic domperidone fails to increase striatal spiperone binding sites despite hyperprolactinemia: comparison with chronic haloperidol.
Mice were administered the dopaminergic antagonists haloperidol or domperidone in their drinking water for 2 or 21 days. Serum prolactin levels and striatal 3H-spiperone-binding sites (D-2 receptors) were compared to vehicle-treated controls. While only domperidone elevated serum prolactin levels, only haloperidol increased the density of striatal 3H-spiperone-binding site. The failure of domperidone, a potent D-2 receptor antagonist, to increase striatal receptor number is attributed to its poor penetration of the blood-brain barrier. These results indicate that peripheral effects of neuroleptic drugs, including prolactin elevation, are not sufficient for the development of dopaminergic supersensitivity in the central nervous system.
D000818:Animals; D002090:Butyrophenones / Q000378:metabolism*; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004294:Domperidone / Q000494:pharmacology*; D006220:Haloperidol / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011388:Prolactin / Q000097:blood*; D011954:Receptors, Dopamine / Q000187:drug effects* / Q000378:metabolism; D013134:Spiperone / Q000378:metabolism*
D002090:Butyrophenones; D011954:Receptors, Dopamine; C031611:spiroperidol receptor; D013134:Spiperone; D004294:Domperidone; D011388:Prolactin; D006220:Haloperidol