Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 296, Issue 2, pp 117–121 | Cite as

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

  • G. Biggio
  • A. Guidotti
  • E. Costa


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.

Key words

Cerebellum cGMP Morphine Mossy fibers Climbing fibers Striatum 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Allen, G. I., Tsukahara, N. T.: Cerebrocerebellar communication systems. Physiol. Rev. 14, 957–1006 (1974)Google Scholar
  2. Biggio, G., Guidotti, A.: Climbing fibers activation and 3,5-cyclic guanosine monophosphate (cGMP) content in cortex and deep nuclei of cerebellum. Brain Res. 107, 365–373 (1976)Google Scholar
  3. Biggio, G., Guidotti, A., Costa, E.: GABA activation mediates the decrease of cerebellar cGMP elicited by diazepam. Proc. nat. Acad. Sci. (Wash.) (in press, 1977)Google Scholar
  4. Carenzi, A., Cheney, D. L., Costa, E., Guidotti, A., Racagni, G.: Action of opiates, antipsychotics, amphetamine and apomorphine on dopamine receptors in rat striatum: in vivo changes of 3′,5′-cyclic adenosine monophosphate content and acetylcholine turnover rate. Neuropharmacology 14, 927–939 (1975)Google Scholar
  5. Clement-Cormier, Y. C., Kebabian, J. W., Petzold, G. L., Greengard, P.: Dopamine sensitive adenylate cyclase in mammalian brain: a possible site of action of antipsychotic drug. Proc. nat. Acad. Sci. (Wash.) 71, 1113–1117 (1974)Google Scholar
  6. Costal, B., Olley, J. E.: Cholinergic and neuroleptic-induced catalepsy: modification by lesions in the caudate-putamen. Neuropharmacology 10, 297–306 (1971)Google Scholar
  7. D'Amour, F. E., Smith, D. L.: A method of determining loss of pain sensation. J. Pharmacaol. exp. Ther. 72, 74–79 (1941)Google Scholar
  8. Desclin, J. G., Escubi, J.: Effects of 3-acetylpyridine on the central nervous system of the rat, as demonstrated by silver methods. Brain Res. 77, 349–364 (1974)Google Scholar
  9. Dill, R., Costa, E.: Behavioral dissociation on the enkaphalinergic systems of nuclei accumbens and caudatus. Neuropharmacology (in press, 1977)Google Scholar
  10. Filburn, C. R., Karn, J.: An isotopic assay of cyclic 3′-5′-nucleotide phosphodiesterase with aluminum oxide columns. Analyt. Biochem. 52, 505–516 (1973)Google Scholar
  11. Fox, M., Williams, I. D.: The caudate nucleus-cerebellar pathways: an electrophysiological study of their route through the midbrain. Brain Res. 20, 140–144 (1970)Google Scholar
  12. Guidotti, A., Cheney, D. L., Trabucchi, M., Doteuchi, M., Wang, C., Hawkins, R. A.: Focussed microwave radiation: a technique to minimize post mortem changes of cyclic nucleotides, dopa and choline and to preserve brain morphology. Neuropharmacology 13, 1115–1122 (1974)Google Scholar
  13. Gullis, R., Traber, J., Hamprecht, B.: Morphine elevates levels of cyclic GMP in a neuroblastoma X glioma hybrid cell line. Nature (Lond.) 256, 57–59 (1975)Google Scholar
  14. Harper, J. F., Brooker, C.: Femtomole sensitive radioimmunoassay for cyclic AMP and cyclic GMP after 2'0-acetylation by acetic anhydride in aqueous solution. J. Cyclic Nucleotide Res. 1, 207–218 (1975)Google Scholar
  15. Ito, M., Yoshida, M., Obata, K., Kawai, N., Udo, M.: Inhibitory control of intracerebellar nuclei by Purkinje cell axons. Exp. Brain Res. 10, 64–80 (1970)Google Scholar
  16. Kemp, J. M., Powell, T. P. S.: The connections of the striatum and globus pallidus: synthesis and speculations. Phil. Trans. B 13, 262, 441–457 (1971)Google Scholar
  17. Koslow, S. H., Schlumpf, M.: Quantitation of adrenaline in rat brain nuclei and areas by mass fragmentography. Nature (Lond.) 251, 530–531 (1974)Google Scholar
  18. Litchfield, J. T., Wilcoxon, F.: A simplified method of evaluating dose effect experiments. J. Pharmacol. exp. Ther. 96, 99–113 (1949)Google Scholar
  19. Lowry, O. H., Rosebrough, N. J., Farr, A. L., Randall, R. J.: Protein measurement with the Folin phenol reagent. J. biol. Chem. 193, 265–275 (1951)Google Scholar
  20. Mao, C. C., Guidotti, A.: Simultaneous isolation of adenosine 3′,5′ cyclic monophosphate (cAMP) and guanosine 3,5 cyclic monophosphate (cGMP) in small tissue samples. Analyt. Biochem. 59, 63–68 (1974)Google Scholar
  21. Mao, C. C., Guidotti, A., Landis, S.: Cyclic GMP: reduction of cerebellar concentration in nervous mutant mice. Brain Res. 90, 335–339 (1975)Google Scholar
  22. Minneman, K. P., Iversen, L. L.: Enkephalin and opiate narcotics increase cGMP accumulation in slices of rat neostriatum. Nature (Lond.) 262, 313–314 (1976)Google Scholar
  23. Pellegrino, L., Dushman, A. J.: A stereotaxic atlas of the rat brain. New York: Appleton Century Crafts 1967Google Scholar
  24. Pert, C. B., Snyder, S. H.: Opiate receptor: demonstration in nervous system tissue. Science 179, 1011–1014 (1973)Google Scholar
  25. Racagni, G., Zsilla, G., Guidotti, A., Costa, E.: Accumulation of cGMP in striatum of rats injected with narcotic analgesics: antagonism by naltrexone. J. Pharm. Pharmacol. 28, 258–260 (1976)Google Scholar

Copyright information

© Springer-Verlag 1977

Authors and Affiliations

  • G. Biggio
    • 1
  • A. Guidotti
    • 1
  • E. Costa
    • 1
  1. 1.Laboratory of Preclinical PharmacologyNational Institute of Mental Health, Saint Elizabeths HospitalWashington, D.C.USA

Personalised recommendations