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Effects of psychotropic drugs on the distribution of 3H-dopamine into compartments of rat striatal synaptosomes and on subsequent depolarization-induced 3H-dopamine release

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Summary

The effects of various drugs on the distribution of 3H-dopamine in rat striatal synaptosomes were studied after superfusion with this radiolabelled neurotransmitter. By compartmental analysis of the efflux of radioactivity, drug effects on the total accumulation of 3H-dopamine, on the “bound fraction” and on the rate constant of the efflux of radioactivity from the tissue were determined. Subsequently, the synaptosomes were exposed to 40 mM K+, in order to assess also the effects of these drugs on depolarization-induced 3H-dopamine release.

The results show that:

  1. 1.

    Reserpine strongly diminished K+-induced 3H-dopamine release and prevented the retention of 3H-dopamine as a bound fraction, confirming that this compartment represents vesicular storage of 3H-dopamine.

  2. 2.

    Just like cocaine, the uptake inhibitors nomifensine and benztropine did not affect the distribution of accumulated 3H-dopamine into synaptosomal compartments and had no effect on the fraction of 3H-dopamine released upon K+-depolarization. At relatively high concentrations, in the micromolar range these drugs displayed efflux-enhancing properties.

  3. 3.

    Both tyramine and (+)-amphetamine strongly affected the intrasynaptosomal distribution of 3H-dopamine and increased the efflux rate constant of radioactivity. However, in contrast to tyramine, (+)-amphetamine affected the K+-induced 3H-dopamine release to a greater extent than the bound fraction, which suggests a preferential effect of this drug on the releasable 3H-dopamine pool.

  4. 4.

    In micromolar concentrations, neuroleptic drugs only weakly inhibited the 3H-dopamine accumulation, but enhanced the rate constant of the efflux of radioactivity, presumably by interfering with vesicular 3H-dopamine storage.

It is concluded that with the approach used in the present study, a relable distinction between uptake-inhibiting and releasing effects of drugs can be made.

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  1. Department of Pharmacology, Free University, Medical Faculty, Van der Boechorststraat 7, NL-1081 BT, Amsterdam, The Netherlands

    Cees D. J. de Langen & Arie H. Mulder

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  1. Cees D. J. de Langen
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  2. Arie H. Mulder
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de Langen, C.D.J., Mulder, A.H. Effects of psychotropic drugs on the distribution of 3H-dopamine into compartments of rat striatal synaptosomes and on subsequent depolarization-induced 3H-dopamine release. Naunyn-Schmiedeberg's Arch. Pharmacol. 311, 169–177 (1980). https://doi.org/10.1007/BF00510256

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  • DOI: https://doi.org/10.1007/BF00510256

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