enalaprilat-anhydrous and zabicipril

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.

Topics: 3,4-Dihydroxyphenylacetic Acid; Adrenergic alpha-Agonists; Adrenergic alpha-Antagonists; Adrenergic beta-Agonists; Adrenergic beta-Antagonists; Animals; Bridged Bicyclo Compounds; Bridged Bicyclo Compounds, Heterocyclic; Clonidine; Electrophysiology; Enalaprilat; Extracellular Space; Hydroxyindoleacetic Acid; Locus Coeruleus; Neurons; Norepinephrine; Raphe Nuclei; Rats; Rats, Wistar; Serotonin