Differential actions of diazepam on the release of [3H]5-hydroxytryptamine from cortical and midbrain raphe slices in the rat.
The possible interaction of the benzodiazepine diazepam with synaptic mechanisms of the central neurotransmitter 5-hydroxytryptamine (5-HT) has been studied in the rat using the superfusion in vitro release technique. The effect of diazepam (1-100 microM) on the spontaneous and potassium-induced release of radioactivity from superfused slices preloaded with [3H]5-HT prepared from cerebral cortex (fronto-parietal) and midbrain raphe region was monitored and compared. The results demonstrate a differential action of diazepam on the release of cortical and raphe 5-HT. In cerebral cortex diazepam significantly reduces both spontaneous and potassium-evoked release of [3H]5-HT. Conversely in raphe slices diazepam significantly enhances both spontaneous and potassium-evoked release of [3H]5-HT. In both tissues the effect of diazepam on K+-stimulated neurotransmitter release was abolished in the presence of picrotoxin. The experiments suggest that the effects of benzodiazepines on 5-HT mechanisms may be manifested at least in part through gamma-aminobutyric acid receptors.
D000818:Animals; D001933:Brain Stem / Q000378:metabolism*; D002118:Calcium / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D003975:Diazepam / Q000494:pharmacology*; D004347:Drug Interactions; D008297:Male; D010852:Picrotoxin / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D011903:Raphe Nuclei / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D012701:Serotonin / Q000378:metabolism*; D013997:Time Factors
D002118:Calcium; D003975:Diazepam; D010852:Picrotoxin; D011188:Potassium; D012701:Serotonin