Reserpine-induced reduction of in vivo binding of SCH 23390 and N-methylspiperone and its reversal by d-amphetamine.
In order to clarify the role of endogenous dopamine in the binding of [3H]SCH23390 and [3H]N-methylspiperone to the mouse striatum in vivo, the effects of reserpine and the reversal of these effects by d-amphetamine were investigated. Radioactivity was measured in the striatum and cerebellum following i.v. injection of each ligand into control and drug-treated mice. The ratio of radioactivity in the striatum to that in the cerebellum, plotted as a function of time, showed a linear correlation. Pretreatment with reserpine 24 h prior to injection of tracer significantly decreased the in vivo binding of both [3H]SCH23390 and [3H]N-methyl-spiperone in a dose-dependent manner. Saturation experiments indicated that these changes in in vivo binding were due mainly to changes in apparent affinity rather than to the number of binding sites available. Administration of d-amphetamine to reserpine-treated mice reversed the effect of reserpine in a dose-dependent manner. Blockade of dopamine D1 receptors with SCH23390 did not prevent the reversal by d-amphetamine of [3H]N-methylspiperone binding in vivo; however, treatment with haloperidol did prevent the effect of d-amphetamine on [3H]SCH23390 binding. These results suggest that dopamine D2 receptor-mediated neurotransmission might itself regulate the binding of dopamine to receptors in vivo.
Inoue
O
O
Division of Clinical Research, National Institute of Radiological Sciences, Chibashi, Japan.
Tsukada
H
H
Yonezawa
H
H
Suhara
T
T
Langstrom
B
B
D000818:Animals; D001552:Benzazepines / Q000378:metabolism*; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D003913:Dextroamphetamine / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D051379:Mice; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism; D012110:Reserpine / Q000494:pharmacology*; D013134:Spiperone / Q000031:analogs & derivatives* / Q000378:metabolism
D001552:Benzazepines; D011954:Receptors, Dopamine; D013134:Spiperone; C039167:3-N-methylspiperone; D012110:Reserpine; D003913:Dextroamphetamine