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α2-Adrenoceptor modulation of rat ventral hippocampal 5-hydroxytryptamine release in vivo

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Summary

The putative existence of a functional α2-adrenoceptor-mediated modulation of 5-HT release in vivo from serotonergic neuronal terminals in the ventral hippocampus was investigated using intracerebral microdialysis in chloral hydrate-anaesthetised rats. The α2-adrenoceptor agonist clonidine (0.01–0.3 mg/kg, SC) dose-dependently decreased the 5-HT output. The response to clonidine was antagonized by systemic or local administration of the α2-adrenoceptor antagonist idazoxan (0.1 mg/kg, SC, or 10 µmol/l, via the dialysis perfusion medium). Similarly, the 5-HT release-suppressing response to the thiazole α2-adrenoceptor agonist jingsongling (0.1 mg/kg, SC) was blocked by idazoxan (0.1 mg/kg, SC). The mixed β-adrenoceptor/5-HT1 receptor antagonist pindolol (8.0 mg/kg, SC) did not affect the clonidine-induced reduction of 5-HT release. Tyrosine hydroxylase inhibition by means of α-methyl-para-tyrosine (α-MT; 250 mg/kg, IP) caused a drastic reduction (>80%) in dialysate 3,4-dihydroxyphenyl acetic acid (DOPAC) output but did not affect the 5-HT output per se over 3 h post-injection. Nor did the α-MT pretreatment prevent, but instead significantly enhanced, the 5-HT release-suppressing effect of clonidine. The results demonstrate that the release of 5-HT from serotonergic nerve terminals in rat ventral hippocampus in vivo is modulated by α2-adrenoceptors, probably both by heteroreceptors on the axon terminals of the serotonergic neurones and by other α2-adrenoceptor sites situated pre- and/or postsynaptic to the noradrenergic terminals. Our results also suggest that while functionally operative, these sites may receive little physiological tone, at least in chloral hydrate-anaesthetised rats.

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  1. Department of Pharmacology, University of Göteborg, P.O. Box 33031, S-40033, Göteborg, Sweden

    Rui Tao & Stephan Hjorth

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  1. Rui Tao
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  2. Stephan Hjorth
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Tao, R., Hjorth, S. α2-Adrenoceptor modulation of rat ventral hippocampal 5-hydroxytryptamine release in vivo. Naunyn-Schmiedeberg's Arch Pharmacol 345, 137–143 (1992). https://doi.org/10.1007/BF00165728

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  • DOI: https://doi.org/10.1007/BF00165728

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