Effects of the GABAergic system on in vivo binding of [3H]N-methylspiperone.
The effects of flunitrazepam, a benzodiazepine receptor agonist and those of NNC-711, a GABA transporter blocker, on the in vivo binding of [3H]N-methylspiperone, a dopamine D2 receptor antagonist, were investigated in mouse brain. Treatment with either flunitrazepam or NNC-711 reduced the specific binding of [3H]N-methylspiperone in the striatum. Flumazenil, a central benzodiazepine receptor antagonist, blocked the effect of flunitrazepam, indicating that the reduction in specific binding in the striatum was mediated via the GABAergic system. The flunitrazepam significantly decreased the specific binding of [3H]N-methylspiperone in the striatum at all time points studied after tracer injection, whereas specific binding in the cerebellum and cerebral cortex was unaltered. This decrease in specific binding in the striatum was found to be due to a reduced input rate constant (k3) of [3H]N-methylspiperone. The maximum number of the binding sites available for dopamine D2 receptors in the striatum was not changed by the flunitrazepam treatment.
Division of Tracer Kinetics, Biomedical Research Center, Osaka University Medical School, Suita, Japan.
T
T
Nakano
K
K
Kobayashi
R
R
Hosoi
S
S
Wakahara
Y
Y
Watanabe
T
T
Nishimura
O
O
Inoue
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D018491:Dopamine Agonists / Q000378:metabolism*; D005445:Flunitrazepam / Q000494:pharmacology*; D018755:GABA Agonists / Q000494:pharmacology*; D008297:Male; D051379:Mice; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism; D014179:Neurotransmitter Uptake Inhibitors / Q000494:pharmacology*; D009557:Nipecotic Acids / Q000494:pharmacology*; D010091:Oximes / Q000494:pharmacology*; D017447:Receptors, Dopamine D1 / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D018079:Receptors, GABA / Q000187:drug effects / Q000502:physiology*; D011963:Receptors, GABA-A / Q000187:drug effects / Q000502:physiology*; D013134:Spiperone / Q000031:analogs & derivatives* / Q000378:metabolism; D014316:Tritium
D018491:Dopamine Agonists; D018755:GABA Agonists; D014179:Neurotransmitter Uptake Inhibitors; D009557:Nipecotic Acids; D010091:Oximes; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D018079:Receptors, GABA; D011963:Receptors, GABA-A; D014316:Tritium; C078793:NNC 711; D013134:Spiperone; D005445:Flunitrazepam; C039167:3-N-methylspiperone