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GABAB receptor-mediated inhibition of serotonin release in the rat brain

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Summary

Rat brain frontal cortex or striatal slices preincubated with 3H-serotonin were superfused with physiological salt solution and tritium overflow was evoked by electrical field stimulation at a frequency of 3 Hz.

  1. 1.

    GABA 1 mmol/l inhibited the evoked overflow from frontal cortex slices by about 30%. The inhibitory effect was abolished when the frequency of electrical stimulation was 10 instead of 3 Hz. Progabide and R(−)-baclofen were more potent, whereas muscimol was less potent than GABA itself in inhibiting the evoked overflow; the IC15 values of progabide, R(−)-baclofen, GABA and muscimol were 8.3, 15, 170 and >320 μmol/l, respectively. S(+)-baclofen behaved as a partial agonist with a maximum inhibitory effect by about 15%. Nipecotic acid and aminooxyacetic acid were ineffective. The same held true for bicuculline, picrotoxin and diazepam.

  2. 2.

    Bicuculline, picrotoxin, diazepam, phentolamine and the serotonin receptor antagonist metitepin did not influence the inhibitory effect of GABA. By contrast, S(+)-baclofen attenuated the effects of GABA and R(−)-baclofen.

  3. 3.

    The evoked overflow from striatal slices was inhibited by GABA and progabide (IC15 values: 480 and 13 μmol/l, respectively). Nipecotic acid was ineffective.

The results suggest that exogenous GABA inhibits serotonin release in the rat brain via GABAB receptors which may be assumed to be located presynaptically.

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Authors and Affiliations

  1. Pharmakologisches Institut der Universität Essen, Hufelandstrasse 55, D-4300, Essen 1, Federal Republic of Germany

    E. Schlicker, K. Classen & M. Göthert

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  1. E. Schlicker
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  2. K. Classen
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  3. M. Göthert
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This study was supported by a grant of the Deutsche Forschungsgemeinschaft

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Schlicker, E., Classen, K. & Göthert, M. GABAB receptor-mediated inhibition of serotonin release in the rat brain. Naunyn-Schmiedeberg's Arch. Pharmacol. 326, 99–105 (1984). https://doi.org/10.1007/BF00517304

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  • DOI: https://doi.org/10.1007/BF00517304

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