Changes in serotonin metabolism in the rat raphe magnus and cardiovascular modifications following systemic administration of clonidine and other central alpha 2-agonists: an in vivo voltammetry study.
By using the in vivo voltammetry, it was demonstrated that an injection of clonidine induced both cardiovascular modifications (hypotension and bradycardia) and a decrease in the level of 5-hydroxyindolacetic acid (5-HIAA) in the ventromedial B3 serotonergic (5-HT) cell bodies of the medulla oblongata of the rat. The cardiovascular effects of clonidine and of two other imidazolic compounds (detomidine and medetomidine) are likely to be related to their alpha 2 adrenoceptor agonist properties since hypotension and bradycardia were completely antagonized by idazoxan. The decrease in levels of 5-HIAA, induced by these three imidazolic compounds is likely to represent the combination of two additional mechanisms: (i) the stimulation of the alpha 2 adrenoceptors which could contribute to 55% of the decrease observed for the extracellular 5-HIAA and (ii) the interaction with a non-alpha 2 site (through a putative imidazole recognition site), corresponding to the part of the decrease (about 45%) which was not prevented by idazoxan.
Aslanian
V
V
Laboratoire de Neuropharmacologie CNRS UMR 12, Faculté de Pharmacie, Lyon, France.
Renaud
B
B
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003000:Clonidine / Q000494:pharmacology*; D004146:Dioxanes / Q000494:pharmacology; D004563:Electrochemistry; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D019329:Idazoxan; D007093:Imidazoles / Q000494:pharmacology; D007150:Immunohistochemistry; D008297:Male; D020926:Medetomidine; D011903:Raphe Nuclei / Q000033:anatomy & histology / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism*
D000316:Adrenergic alpha-Agonists; D004146:Dioxanes; D007093:Imidazoles; D012701:Serotonin; C041255:detomidine; D003000:Clonidine; D020926:Medetomidine; D019329:Idazoxan