On the mechanism of the decrease in cerebellar cyclic GMP content elicited by opiate receptor agonists

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Abstract
Summary Morphine, dextromoramide (4 μmol/kg i.p.) and vimonol R2 (17 μmol/kg i.p.) in analgesic doses (28 to 112 μmol/kg i.p.) decreased 3′,5′-cyclic guanosine monophosphate (cGMP) in rat cerebellar cortex; morphine also decreased the cGMP content in deep cerebellar nuclei. Intrastriatal but not intracerebellar injections of morphine (20 μg) decreased cerebellar cGMP content. Naltrexone, an opiate receptor antagonist, but not apomorphine, a dopaminergic receptor agonist, blocked the effect of morphine on cerebellar cGMP. Pretreatment with 3-acetylpyridine (3-AP) which destroys the climbing fibers, failed to antagonize the effect of morphine on cerebellar cGMP. These results suggest that activation of opiate receptors in striatum decreases cerebellar cGMP content presumably by reducing activity in the mossy fiber excitatory input to cerebellum.