Abstract
5-Hydroxytryptamine (5-HT) receptors of the 5-HT 1A subtype are localized on serotoninergic cells and dendrites in the raphe nuclei of the brain stem and are believed to regulate synaptic 5-HT release through an inhibitory influence on serotoninergic impulse flow. The effects of 5-HT 1A agonists on 5-HT release can, therefore, only be detected by measurement of 5-HT release from intact serotoninergic neurones. Here we review the evidence that the microdialysis technique, when applied to the anaesthetized rat, is able to detect extracellular 5-HT in the brain which derives from serotoninergic neurones and changes in accordance with serotoninergic neuronal activity. We have observed that a range of 5-HT 1A agonists, including 8-hydroxy-2-(di- n-propylamino) tetralin (8-OH-DPAT), inhibit 5-HT release in hippocampus, most probably by acting on somatodendritic 5-HT 1A autoreceptors in the dorsal raphe nucleus. The inhibitory action of 8-OH-DPAT and several other selective 5-HT 1A receptor active drugs on 5-HT release is sensitive to pindolol, further supporting the idea that the 5-HT receptor being measured is of the 5-HT 1 subtype. Two drugs, BMY 7378 and NAN-190, which show 5-HT 1A antagonist properties in certain models, reduce 5-HT release indicating that they have mixed agonist/antagonist actions at the 5-HT 1A receptor. Our data indicate that measurement of 5-HT release in rat brain using the microdialysis technique may be a useful method to probe the pharmacology of the 5-HT 1A autoreceptor in vivo.
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