The present study was designed to test whether chronic neuroleptic treatment, which is known to alter both expression and density of dopamine D 2 receptors in striatal regions, has effects upon function and binding level of the cannabinoid CB 1 receptor in the basal ganglia by using receptor autoradiography. As predicted, subchronic haloperidol treatment resulted in increased binding of 3 Hraclopride and quinpirole-induced guanosine 5 0 -O-(g-[ 35 S]thio)triphosphate ([ 35 S]GTPgS) in the striatum when compared to that measured in control animals. This increased D 2 receptor binding and function after 3 days washout was normalized after a 2-week washout period. Effect of haloperidol treatment was studied for CB 1 receptor binding and CP55,940-stimulated [ 35 S]GTPgS in the striatum, globus pallidus, and substantia nigra.
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[H]CP55,940 binding levels were found in rank order from highest to lowest in substantia nigra > globus pallidus > striatum. Furthermore, subchronic haloperidol treatment resulted in elevated binding levels of 3 [H]CP55,940 in the striatum and the substantia nigra and CB 1 receptor-stimulated [ 35 S]GTPgS bindings in the substantia nigra after 3 days washout. These increased binding levels were normalized at 1-4 weeks after termination of haloperidol treatment. Haloperidol treatment had no significant effect on CB 1 receptor or [ 35 S]GTPgS binding levels in globus pallidus. The results help to elucidate the underlying biochemical mechanism of CB 1 receptor supersensitivity after haloperidol treatment. V