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.