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Inhibition of 5-hydroxytryptamine neuronal activity by the 5-HT agonist, DOI

Garratt, J. C., Kidd, Emma ORCID:, Wright, I. K. and Marsden, C. A. 1991. Inhibition of 5-hydroxytryptamine neuronal activity by the 5-HT agonist, DOI. European Journal of Pharmacology 199 (3) , pp. 349-355. 10.1016/0014-2999(91)90499-G

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Systemic, intra-raphe and microiontophoretic administration of the 5-hydroxytryptamine (5-HT)IC/5-HT2 agonist (1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) inhibited the firing of 5-HT neurones in the dorsal raphe. DOI administered systemically and directly into the raphe also decreased the extracellular concentration of 5-hydroxytryptamine (5-HT) in the frontal cortex. In contrast, the administration of DOI directly into the frontal cortex did not significantly alter the concentration of frontal cortical extracellular 5-HT. The reduction of the firing rate of 5-HT neurones in the dorsal raphe and extracellular 5-HT concentration in the frontal cortex induced by systemic administration of DOI could not be blocked by the 5-HT2 antagonist ketanserin, ritanserin (5-HT2/5-HTIC antagonist) or the putative 5-HT1A antagonist, pindolol. These results suggest that the inhibition of 5-HT neuronal firing seen with administration of DOI is mediated via an action within the dorsal raphe and at least in close proximity to the 5-HT neurone cell bodies. The decrease in frontal cortical extracellular concentration of 5-HT release was not due to a direct action in the frontal cortex itself and may possibly be as a result of the decrease in the firing rate of the 5-HT neurones in the dorsal raphe. The mechanism of action of DOI to produce these effects is, however, unclear and warrants further investigation.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Pharmacy
Subjects: R Medicine > RM Therapeutics. Pharmacology
Uncontrolled Keywords: DOI (1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane); Dorsal raphe; Frontal cortex; Neuronal firing; 5-HT release
Publisher: Elsevier
ISSN: 0014-2999
Last Modified: 18 Oct 2022 13:38

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