Skip to main content
Log in

Effects of dopaminergic stimulants on cyclic nucleotide levels in mouse brain in vivo

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

Summary

Dopaminergic stimulants (amantadine, amphetamine, apomorphine, nomifensine and L-dopa plus benserazide) increased cyclic GMP levels in the medial forebrain and cerebellum of mice. Cyclic AMP levels were not significantly altered under these conditions. Drug-induced stereotyped behaviour correlated in intensity and duration to the changes in cyclic GMP levels in the medial forebrain.

Amantadine, apomorphine and nomifensine showed a linear dose response relationship, but differed as to the extent and time course of the increase in cyclic GMP. Amantadine and apomorphine were more effective in elevating cyclic GMP in the medial forebrain than in the cerebellum. Amphetamine produced an exponential dose-related elevation of cyclic GMP in both parts of the brain, being more effective in the cerebellum than in the medial forebrain at high doses, thus indicating a complex mechanism of action.

L-Dopa (50 mg/kg) and benserazide (40 mg/kg) alone did neither significantly increase cyclic GMP levels nor induce stereotyped behaviour. However, in animals pretreated with benserazide (15 min prior to L-dopa) L-dopa produced a significant elevation of cyclic GMP and stereotyped behaviour.

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

  • Andén, N. E., Fuxe, K., Hamberger, D., Hökfeldt, A.: A quantitative study of the nigro-neostriatal dopamine neurons system in the rat. Acta physiol. scand. 67, 306–312 (1966)

    Google Scholar 

  • Bucher, M. B., Schorderet, M.: Apomorphine-induced accumulation of cyclic AMP in isolated retinas of the rabbit. Biochem. Pharmacol. 23, 3079–3082 (1974)

    Google Scholar 

  • Costall, B., Kelly, D. M., Naylor, R. J.: Nomifensine: A potent dopaminergic agonist of antiparkinson potential. Psychopharmacologia (Berl.) (in press, 1976)

  • 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 

  • Fox, M., Williams, T. D.: Responses evoked in the cerebellar cortex by stimulation of the caudate nucleus in the cat. J. Physiol. (Lond.) 198, 435–450 (1968)

    Google Scholar 

  • Fox, M., Williams, T. D.: The caudate nucleus-cerebellar pathways: an electrophysiological study of their route through the midbrain. Brain Res. 20, 140–144 (1970)

    Google Scholar 

  • Gerhards, H. J., Carenzi, A., Costa, E.: Effect of nomifensine on motor activity, dopamine turnover rate and cyclic 3′,5′-adenosine monophosphate concentrations of rat striatum. Naunyn-Schmiedeberg's Arch. Pharmacol. 286, 49–63 (1974)

    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: Advances in cyclic nucleotide research, vol. 3 (P. Greengard and G. A. Robison, eds.), pp. 155–223. New York: Raven Press, 1973

    Google Scholar 

  • Iwatsubo, K., Clouet, D. H.: Dopamine-sensitive adenylate cyclase of the caudate nucleus of rats treated with morphine or haloperidol. Biochem. Pharmacol. 24, 1499–1503 (1975)

    Google Scholar 

  • Kebabian, J. W., Greengard, P.: Dopamine-sensitive adenylate cyclase: Possible role in synaptic transmission. Science 174, 1346–1349 (1971)

    Google Scholar 

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

    Google Scholar 

  • Kebabian, J. W., Steiner, A. L., Greengard, P.: Muscarinic cholinergic regulation of cyclic guanosine 3′,5′-monophosphate in autonomic ganglia: Possible role in synaptic transmission. J. Pharmacol. exp. Ther. 193, 474–488 (1975)

    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 

  • Miller, R., Horn, A., Iversen, L., Pinder, R.: Effects of dopamine-like drugs on rat striatal adenyl cyclase have implications for CNS dopamine receptor topography. Nature (Lond.) 250, 238–241 (1974)

    Google Scholar 

  • Opmeer, F. A., Gumulka, S. W., Dinnendahl, V., Schönhöfer, P. S.: Effects of central excitatory and depressant drugs on cyclic guanosine 3′,5′-monophosphate and adenosine 3′,5′-monophosphate levels in mouse brain. Naunyn-Schmiedeberg's Arch. Pharmacol. (in press, 1976)

  • Reis, D. J.: Central noradrenergic neurons. Advanc. Neurol. 5, 45–56 (1975)

    Google Scholar 

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

    Google Scholar 

  • Ungerstedt, U.: 6-Hydroxydopamine-induced degeneration of central monoamine neurons. Europ. J. Pharmacol. 5, 107–110 (1968)

    Google Scholar 

  • Ungerstedt, U.: Stereotaxic mapping of monoamine pathways in the rat brain. Acta physiol. scand. 82, (Suppl. 367) 1–48 (1971)

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Gumulka, S.W., Dinnendahl, V., Peters, H.D. et al. Effects of dopaminergic stimulants on cyclic nucleotide levels in mouse brain in vivo. Naunyn-Schmiedeberg's Arch. Pharmacol. 293, 75–80 (1976). https://doi.org/10.1007/BF00498873

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00498873

Key words

Navigation