Brainstem serotonin receptors in the guinea pig: Implications for myoclonus
The brainstem is the locus of serotonin (5-HT)-mediated myoclonus in the guinea pig, which is induced by 5-hydroxy-l-tryptophan (l-5-HTP) and indole but not piperazine 5-HT receptor agonists. As an initial step in testing the hypothesis that one 5-HT receptor subtype mediates this effect, we measured seven 5-HT receptor binding sites and the 5-HT uptake site in guinea pig brainstem and compared them to the rat. In guinea pig brainstem, the rank order of binding site density was: 5-HT transporter site@?5-HT 1D > antagonist-labeled 5-HT 2 > 5-HT 1A , 5-HT 1C > 5-HT 1E > agonist-labeled 5-HT 2 binding site. There were fewer 5-HT 1A and 5-HT 1C binding sites and 5-HT uptake sites in guinea pig than rat brainstem, more 5-HT 1D and antagonist-labeled 5-HT 2 sites, but the differences were 2-fold or less. The major species difference was that 5-HT 1B sites were virtually undetectable in guinea pig brainstem. Limited competition experiments with related 5-HT receptor subtype-selective agonists and antagonists suggested that the sites in guinea pig brainstem conformed to those described in the rat. 5-HT agonist and antagonist dose-threshold and dose maximum-effect data from guinea pig myoclonus in vivo were compared with receptor affinities at each receptor site in vitro from the literature. No convincing correlation between myoclonus and one particular 5-HT site was found. These data indicate the presence of a full complement of 5-HT receptor binding site subtypes in guinea pig brainstem with some species differences. However, EC 50 data and use of more selective drugs in behavioral experiments will be necessary to establish the relation between these binding sites and myoclonus.
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