Involvement of 5-HT1A- and alpha 2-receptors in the decreased 5-hydroxytryptamine release and metabolism in rat suprachiasmatic nucleus after intravenous 8-hydroxy-2-(n-dipropylamino) tetralin

Abstract

The 5-hydroxytryptamine1A-receptor agonist 8-hydroxy-2-(n-dipropylamino) tetralin (8-OH-DPAT, 0.1 mg kg-1 i.v.) decreased the height of the extracellular 5-hydroxyindoleacetic acid (5-HIAA) oxidation peak recorded in the suprachiasmatic nucleus (SCN) of the anaesthetized rat by use of differential pulse voltammetry. The decrease in extracellular 5-HIAA produced by 8-OH-DPAT could be partially attenuated by prior administration of the non-selective 5-HT receptor antagonist methiothepin (1 mg kg-1 i.v.). The 5-HT2-receptor antagonist ritanserin (0.2 mg kg-1 i.v.) did not appear to block the effects of 8-OH-DPAT. The selective ligand for 5-HT1A recognition sites TVX Q 7821 (isapirone, 1 mg kg-1 i.v.) decreased the extracellular level of 5-HIAA in the SCN but to a lesser extent than 8-OH-DPAT. The response to 8-OH-DPAT was attenuated by prior administration of TVX Q 7821 to a level suggesting that TVX Q 7821 had blocked the effect of intravenous 8-OH-DPAT. Idazoxan (0.2 mg kg-1 i.v.) an alpha 2-adrenoceptor antagonist, completely blocked the effect of 8-OH-DPAT on the 5-HIAA oxidation peak recorded in the SCN, whilst having no effect on the 5-HIAA oxidation peak when given alone. At a dose of 0.5 mg kg-1 i.v. idazoxan induced a 120% increase in the height of the indole oxidation peak, suggesting that 5-HT release and metabolism in the rat SCN may be influenced by tonic adrenergic inputs. The data in this paper suggest that 5-HT1A- and alpha 2-receptors are involved in the effects of i.v. administered 8-OH-DPAT on 5-HT release and metabolism in the SCN in vivo.