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Opposing actions of D-1 and D-2 dopamine receptor-mediated alterations of adenosine-3′,5′-cyclic monophosphate (cyclic AMP) formation during the amphetamine-induced release of endogenous dopamine in vitro

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Summary

Changes in the formation of cyclic AMP following d-amphetamine (0.1 to 20 pmol/1) were examined in vitro in striatal slices of the rat. d-Amphetamine caused a doserelated increase in cyclic AMP content. This action of d-amphetamine was abolished by tissue pretreatment with reserpine (2.5 mg/kg, i.p.) and 3-iodotyrosine (1 mmol/1). By contrast, both clorgyline (0.1 pmol/l) and nomifensine (30 μmol/l) enhanced the d-amphetamine-induced increase in cyclic AMP formation. In superfusion experiments, a strong correlation between endogenous dopamine and cyclic AMP release was observed before, during and after d-amphetamine exposure. Finally, Sch 23390 (10 μmol/1) abolished while (−)sulpiride (10 μmol/1) enhanced the amphetamine-induced increase in cyclic AMP content. These results suggest that d-amphetamine enhances the formation of cyclic AMP through the release of endogenous dopamine into the synapse where it can interact with both D-1 and D-2 dopamine receptors. These results provide direct evidence that the antagonistic properties of D-1 and D-2 receptors on cyclic AMP formation are apparent at striatal synapses during release of endogenous neuronal dopamine.

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Abbreviations

DA:

dopamine

5-HT:

serotonin

CAMP:

cyclic AMP adenosine-3′,5′-cyclic monophosphate

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Authors and Affiliations

  1. Department of Neurology, 26506, Morgantown, West Virginia, USA

    Albert J. Azzaro & John Luccil

  2. Department of Pharmacology/Toxicology, 26506, Morgantown, West Virginia, USA

    Albert J. Azzaro & John Liccione

  3. Department of Psychiatry/Behavioral Medicine, West Virginia University Medical Center, 26506, Morgantown, West Virginia, USA

    Albert J. Azzaro

Authors
  1. Albert J. Azzaro
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  2. John Liccione
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  3. John Luccil
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Additional information

Supported in part by the West Virginia University Medical Corporation and a grant from the Fraternal Order of Eagles. Some of the findings were presented at the Annual meeting of the Society for Neurosciences, Washington, DC (Azzaro and Liccione 1986)

Send offprint requests to A. J. Azzaro at the above address

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Azzaro, A.J., Liccione, J. & Luccil, J. Opposing actions of D-1 and D-2 dopamine receptor-mediated alterations of adenosine-3′,5′-cyclic monophosphate (cyclic AMP) formation during the amphetamine-induced release of endogenous dopamine in vitro. Naunyn-Schmiedeberg's Arch Pharmacol 336, 133–138 (1987). https://doi.org/10.1007/BF00165796

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  • DOI: https://doi.org/10.1007/BF00165796

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