Effects of idazoxan on dorsal raphe 5-hydroxytryptamine neuronal function.
The effects of the alpha 2-adrenoceptor antagonist idazoxan on 5-hydroxytryptamine (5-HT) neuronal firing and release have been investigated. Idazoxan, administered i.v. (10 micrograms/kg and 0.5 mg/kg) increased dorsal raphe nucleus (DRN)-5-HT neuronal firing rate in a dose-dependent fashion. At the higher dose, a voltammetric study revealed increases in extracellular 5-HT and 5-hydroxyindole acetic acid (5-HIAA) levels, there was no effect with the lower dose. Intra-raphe administration of idazoxan (1 ng) also elevated the firing rate of 5-HT neurones in the dorsal raphe, suggesting that idazoxan may produce the increase in firing by a direct effect in the DRN. However, microiontophoretic application of idazoxan did not increase the firing rate of 5-HT neurones in the DRN. Thus the increase in the firing rate of 5-HT neurones in the DRN observed with systemic and local administration of idazoxan is probably not due to a direct action of idazoxan on the 5-HT neurone. Possibly the idazoxan acted at alpha 2-adrenoceptors located on noradrenergic terminals thus stimulating noradrenaline release and consequently increased 5-HT activity. Chronic administration of idazoxan (0.8 mg/kg per h for 14 days), using osmotic mini-pumps, caused an elevation in basal firing rate and an attenuation of the inhibitory response of DRN 5-HT neurones to the 5-HT1A agonist, 8-hydroxy-2-(di-n-propylamino) tetralin (8-OHDPAT) (10 micrograms/kg i.v.). This finding suggests that chronic infusion with idazoxan leads to desensitisation of the 5-HT1A somatodendritic autoreceptor.
Garratt
J C
JC
Department of Physiology and Pharmacology, Medical School, Queen's Medical Centre, Nottingham, U.K.
Crespi
F
F
Mason
R
R
Marsden
C A
CA
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000317:Adrenergic alpha-Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D000758:Anesthesia; D000818:Animals; D004146:Dioxanes / Q000008:administration & dosage / Q000494:pharmacology*; D004594:Electrophysiology; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D019329:Idazoxan; D066298:In Vitro Techniques; D007276:Injections, Intraventricular; D007478:Iontophoresis; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D011903:Raphe Nuclei / Q000166:cytology / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000502:physiology*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D004146:Dioxanes; D013764:Tetrahydronaphthalenes; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D019329:Idazoxan