Skip to main content
Log in

Effects of stimulatory and depressant drugs on cyclic guanosine 3′,5′-monophosphate and adenosine 3′,5′-monophosphate levels in mouse brain

  • Published:
Naunyn-Schmiedeberg's Archives of Pharmacology Aims and scope Submit manuscript

Summary

Cyclic GMP levels were dose-dependently increased by excitatory drugs such as picrotoxin, pentetrazol, oxotremorine and harmaline in mouse cerebellum and medial forebrain (parts of the cortex, hippocampus, hypothalamus, thalamus, striatum and midbrain) in vivo. Cyclic AMP levels remained unchanged under these conditions. Pretreatment with diazepam completely abolished the effects of picrotoxin and harmaline and significantly reduced the effects of pentetrazol and oxotremorine on cyclic GMP levels, but the tremor due to harmaline and oxotremorine was not blocked. Pretreatment with pentobarbital also prevented or strongly reduced changes in cyclic GMP levels elicited by excitatory drugs without abolishing the tremorigenic effects of harmaline and oxotremorine. Pretreatment with atropine was only effective in blocking cyclic GMP rise and tremor induced by oxotremorine and picrotoxin. Since pentobarbital and diazepam also decreased cyclic GMP levels in a dose-dependent manner in brains of control animals, the changes in cyclic GMP levels observed after administration of excitatory drugs appear to be related to the arousal reaction of the central nervous system.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Bloom, F. E., Stone, T. W., Taylor, D. A.: Responses of identified cerebral cortical neurones to cyclic GMP and cyclic AMP. J. Physiol. 246, 103P-104P (1975)

    Google Scholar 

  • Consolo, S., Ladinsky, H., Peri, G., Garattini, S.: Effect of central stimulants and depressants on mouse brain acetylcholine and choline levels. Europ. J. Pharmacol. 18, 251–255 (1972)

    Google Scholar 

  • Consolo, S., Ladinsky, H., Peri, G., Garattini, S.: Effect of diazepam on mouse whole brain and brain area acetylcholine and choline levels. Europ. J. Pharmacol. 27, 266–268 (1974)

    Google Scholar 

  • Curtis, D. R., Duggan, A. W., Johnston, G. A. R.: Glycine, strychnine, picrotoxin and spinal inhibition. Brain Res. 14, 759–762 (1969)

    Google Scholar 

  • Curtis, D. R., Johnston, G. A. R.: Amino acid transmitters in mammalian central nervous system. Rev. Physiol. Biochem. exp. Pharmacol. 69, 97–188 (1974)

    Google Scholar 

  • Cutler, R. W. P., Dudzinski, D. S.: Effect of pentobarbital on uptake and release of (3H) GABA and (14C) glutamate by brain slices. Brain Res. 67, 546–548 (1974)

    Google Scholar 

  • Cutler, R. W. P., Markowitz, D., Dudzinski, D. S.: The effect of barbiturates on (3H) GABA transport in rat cerebral cortex slices. Brain Res. 81, 189–197 (1974)

    Google Scholar 

  • Dinnendahl, V.: A rapid and simple procedure for the determination of guanosine 3′,5′-monophosphate by use of the protein-binding method. Naunyn-Schmiedeberg's Arch. Pharmacol. 284, 55–61 (1974)

    Google Scholar 

  • Dinnendahl, V.: Effects of stress on mouse brain cyclic nucleotide levels in vivo. Brain Res. 100, 716–719 (1975)

    Google Scholar 

  • Dinnendahl, V., Stock, K.: Effects of arecoline and cholinesterase inhibitors on cyclic guanosine 3′,5′-monophosphate and adenosine 3′,5′-monophosphate in mouse brain. Naunyn-Schmiedeberg's Arch. Pharmacol. 290, 297–306 (1975)

    Google Scholar 

  • Ferrendelli, J. A., Kinscherf, D. A., Kipnis, D. M.: Effects of amphetamine, chlorpromazine and reserpine on cyclic GMP and cyclic AMP levels in mouse cerebellum. Biochem. biophys. Res. Commun. 46, 2114–2120 (1972)

    Google Scholar 

  • Ferrendelli, J. A., Steiner, A. L., McDougal, D. B., Kipnis, D. M.: The effect of oxotremorine and atropine on cGMP and cAMP levels in mouse cerebral cortex and cerebellum. Biochem. biophys. Res. Commun. 41, 1061–1067 (1970)

    Google Scholar 

  • Glowinski, J., Iversen, L. L.: Regional studies of catecholamines in the rat brain. I. The disposition of (3H) norepinephrine, (3H) dopamine and (3H) dopa in various regions of the brain. J. Neurochem. 13, 655–669 (1966)

    Google Scholar 

  • Goldberg, N. D., O'Dea, R. F., Haddox, M. K.: Cyclic GMP. In: Adv. in cyclic nucleotide research, vol. 3 (P. Greengard and G. A. Robison, eds.), pp. 155–223. New York: Raven Press 1973

    Google Scholar 

  • Javoy, F., Agid, Y., Glowinski, J.: Oxotremorine and atropineinduced changes of dopamine metabolism in the rat striatum. J. Pharm. Pharmacol. 27, 677–681 (1975)

    Google Scholar 

  • Kakiuchi, S., Rall, T. W.: The influence of chemical agents on the accumulation of adenosine 3′,5′-phosphate in slices of rabbit cerebellum. Molec. Pharmacol. 4, 367–388 (1968)

    Google Scholar 

  • Kebabian, J. W., Petzold, G. L., Greengard, P.: Dopamine-sensitive adenylate cyclase in caudate nucleus of rat brain and its similarity to the “dopamine receptor”. Proc. nat. Acad. Sci. (Wash.) 69, 2145–2149 (1972)

    Google Scholar 

  • Madan, B. R., Sharma, J. D., Vyas, D. S.: Actions of methaminodiazepoxide on cardiac, smooth and skeletal muscles. Arch. int. Pharmacodyn. 143, 127–137 (1963)

    Google Scholar 

  • Mao, C. C., Guidotti, A., Costa, E.: The regulation of cyclic guanosine monophosphate in rat cerebellum: possible involvement of putative amino acid neurotransmitters. Brain Res. 79, 510–514 (1974a)

    Google Scholar 

  • Mao, C. C., Guidotti, H., Costa, E.: Interactions between γ-aminobutyric acid and guanosine cyclic 3′,5′-monophosphate in rat cerebellum. Molec. Pharmacol. 10, 736–745 (1974b)

    Google Scholar 

  • Mao, C. C., Guidotti, A., Costa, E.: Evidence for an involvement of GABA in the mediation of the cerebellar cGMP decrease and the anticonvulsant action of diazepam. Naunyn-Schmiedeberg's Arch. Pharmacol. 289, 369–378 (1975a)

    Google Scholar 

  • Mao, C. C., Guidotti, A., Costa, E.: Inhibition by diazepam of the tremor and the increase of cerebellar cGMP content elicited by harmaline. Brain Res. 83, 516–519 (1975b)

    Google Scholar 

  • Nicoll, R.: Presynaptic action of barbiturates in the frog spinal cord. Proc. nat. Acad. Sci. (Wash.) 72, 1460–1463 (1975)

    Google Scholar 

  • Posternak, t.: Cyclic AMP and cyclic GMP. Ann. Rev. Pharmacol. 14, 23–33 (1974)

    Google Scholar 

  • Schmidt, M. J., Schmidt, D. E., Robison, G. A.: Cyclic adenosine monophosphate in brain areas: Microwave irridiation as a means of tissue fixation. Science 173, 1142–1143 (1971)

    Google Scholar 

  • Snyder, S. H., Enna, S. J.: The role of central nervous glycine receptors in the pharmacologic actions of benzodiazepines. In: Adv. in biochem. psychopharmacol., vol. 14 (E. Costa and P. Greengard, eds.). New York: Raven Press (in press 1975)

    Google Scholar 

  • Stone, T. W., Taylor, D. A., Bloom, F. E.: Cyclic AMP and cyclic GMP may mediate opposite neuronal responses in the rat cerebral cortex. Science 187, 845–847 (1975)

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Opmeer, F.A., Gumulka, S.W., Dinnendahl, V. et al. Effects of stimulatory and depressant drugs on cyclic guanosine 3′,5′-monophosphate and adenosine 3′,5′-monophosphate levels in mouse brain. Naunyn-Schmiedeberg's Arch. Pharmacol. 292, 259–265 (1976). https://doi.org/10.1007/BF00517387

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00517387

Key words

Navigation