The effect of adrenergic drugs on serotonin metabolism in the nucleus raphe dorsalis of the rat, studied by in vivo voltammetry.
The serotonin (5-HT) and norepinephrine (NE) system participate in the control of behavioural functions. The experiments were aimed at the question whether the NE system of the locus coeruleus interferes with the 5-HT activity of the nucleus raphe dorsalis and of which receptors are possibly involved. The alpha 1- and beta-adrenoceptor agonists methoxamine and isoproterenol, as well as a high dose (600 micrograms/kg i.p.) of the alpha 2-adrenoceptor agonist clonidine, increased extraneuronal 5-hydroxyindoleacetic acid (5-HIAA) levels in the nucleus raphe dorsalis as measured by in vivo voltammetry. In contrast, a low dose (60 micrograms/kg i.p.) of clonidine and the alpha 1-, alpha 2- and beta-adrenoceptor antagonists, prazosin, piperoxane, and atenolol, reduced the 5-HIAA concentration. In the locus coeruleus, the origin of NE projections to the nucleus raphe dorsalis, clonidine decreased whereas piperoxane enhanced extracellular 3,4-dihydroxyphenylacetic acid (DOPAC), an index of NE metabolism in the locus coeruleus. The results suggest that 5-HT neurotransmission in the nucleus raphe dorsalis is stimulated by the NE system of the locus coeruleus and that adrenoceptor drugs may affect 5-HT neuronal activity in addition to NE neurotransmission.
Clement
H W
HW
Department of Neurochemistry, Philipps University, Marburg/Lahn, Germany.
Gemsa
D
D
Wesemann
W
W
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology; D019086:Bridged Bicyclo Compounds, Heterocyclic; D003000:Clonidine / Q000494:pharmacology; D004594:Electrophysiology; D015773:Enalaprilat / Q000494:pharmacology; D005110:Extracellular Space / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008125:Locus Coeruleus / Q000502:physiology; D009474:Neurons / Q000378:metabolism; D009638:Norepinephrine / Q000502:physiology; D011903:Raphe Nuclei / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism*
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D015102:3,4-Dihydroxyphenylacetic Acid; D012701:Serotonin; C065499:zabicipril; D006897:Hydroxyindoleacetic Acid; D015773:Enalaprilat; D003000:Clonidine; D009638:Norepinephrine