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In vivo electrophysiological evidence for tonic activation by endogenous noradrenaline of α2-adrenoceptors on 5-hydroxytryptamine terminals in the rat hippocampus

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Summary

The activation of α2-adrenergic heteroreceptors was studied by comparing the effectiveness of the electrical stimulation of the ascending 5-HT pathway in suppressing the firing activity of CA3 dorsal hippocampus pyramidal neurons prior to, and following, the intravenous administration of noradrenergic agents. Desipramine (2 mg/kg), a selective noradrenaline reuptake blocker, reduced the efficacy of the stimulation; this effect was reversed by the α2-adrenoceptor antagonists yohimbine (0.5 mg/kg) and (-)mianserin (0.5 mg/kg), but not by idazoxan (0.5 mg/kg), an adrenoceptor antagonist with preferential affinity for the imidazoline recognition sites. Low doses of the α2-adrenoceptor agonist clonidine (2 and 10 μg/kg) enhanced the efficacy of the stimulation, while high doses (100 and 400 μg/kg) reduced it. These incremental and decremental effects of clonidine were reversed by 0.1 and 1 mg/kg of yohimbine, respectively. The enhancing effect of the low dose of clonidine (10 μg/kg) was abolished in rats pretreated with the noradrenaline neurotoxin 6-hydroxydopamine. However, the inhibitory effect of a high dose of clonidine (100 μg/kg) was unaltered by this pretreatment. These results indicate that low doses of clonidine preferentially activate α2-adrenergic autoreceptors on the noradrenaline neurons resulting in a reduction of the tonic inhibitory effect of endogenous noradrenaline on 5-HT neurotransmission, while higher doses of clonidine would decrease 5-HT neurotransmission through the direct activation of α2-adrenergic heteroreceptors on 5-HT terminals. Furthermore, the selective α2-adrenergic heteroreceptors antagonist(-)mianserin (0.5 mg/kg) increased by itself the efficacy of 5-HT neurotransmission, an effect not observed with yohimbine and idazoxan. Taken together, these results suggest that, in vivo, the α2-adrenoceptors on 5-HT terminals of the rat hippocampus are tonically activated by endogenous noradrenaline and modulate 5-HT release.

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Authors and Affiliations

  1. Neurobiological Psychiatry Unit, Department of Psychiatry, McGill University, 1033 Pine Avenue West, H3A 1A1, Montréal, Québec, Canada

    Raymond Mongeau, Pierre Blier & Claude de Montigny

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  1. Raymond Mongeau
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  2. Pierre Blier
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  3. Claude de Montigny
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Correspondence to R. Mongeau at the above address

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Mongeau, R., Blier, P. & de Montigny, C. In vivo electrophysiological evidence for tonic activation by endogenous noradrenaline of α2-adrenoceptors on 5-hydroxytryptamine terminals in the rat hippocampus. Naunyn-Schmiedeberg's Arch Pharmacol 347, 266–272 (1993). https://doi.org/10.1007/BF00167444

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  • DOI: https://doi.org/10.1007/BF00167444

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