Facilitation of dopaminergic neural transmission does not affect [11C]SCH23390 binding to the striatal D1 dopamine receptors, but the facilitation enhances phosphodiesterase type‐IV activity through D1 receptors: PET studies in the conscious monkey brain

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Abstract
The present study evaluated the effects of methamphetamine and scopolamine on the striatal dopamine D1 receptor binding, measured by [11C]SCH23390, and D1 receptor‐coupled cAMP messenger system, determined as phosphodiesterase type‐IV (PDE‐IV) activity, were evaluated in the brains of conscious monkeys using positron emission tomography (PET) with microdialysis. When methamphetamine (0.1, 0.3, and 1 mg/kg) or scopolamine (0.01, 0.03, and 0.1 mg/kg) was systemically administered, [11C]SCH23390 binding to D1 receptors was not affected. With administration of methamphetamine, the striatal PDE‐IV activity, as measured with R‐[11C]rolipram (active form) and S‐[11C]rolipram (inactive form), was dose‐dependently facilitated with enhanced dopamine level in the striatal ECF. Administration of scopolamine also induced facilitated PDE‐IV activity without any apparent changes in the ECF dopamine. These facilitations of PDE‐IV activity were abolished by preadministration of SCH23390, but not by raclopride. These results demonstrate that, as evaluated by PDE‐IV activity, the inhibition of muscarinic cholinergic receptors actually facilitated dopamine neuronal signal transduction through D1 receptors, as observed previously on D2 receptors with no apparent increase in the striatal ECF dopamine level, but the enhanced dopamine transmission could not detected by [11C]SCH23390. Synapse 42:258–265, 2001.

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