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The interaction between the locus coeruleus and dorsal raphe nucleus was investigated by means of dual-probe microdialysis in conscious rats. The release of noradrenaline and 5-hydroxytryptamine (5-HT) after inhibition or stimulation of locus cocruleus and dorsal raphe activity was sampled in both nuclei and analysed by high-pressure liquid chromatography (HPLC). The inhibition of locus coeruleus activity by the infusion of the alpha2-adrenoceptor agonist clonidine (100 muM) decreased the release of noradrenaline to 20% in the locus coeruleus and 30% in the dorsal raphe, whilst the release of 5-HT decreased to 80% of control in the two brain areas, The excitation of locus coeruleus activity by the muscarinic receptor agonist carbachol (100 muM) led to an increase in the release of noradrenaline to 240% and 220% of control in the locus coeruleus and dorsal raphe, respectively, The release of 5-HT in both nuclei did not respond to the carbachol infusion into the locus coeruleus. Infusion of the 5-HT1A receptor agonist flesinoxan into the dorsal raphe (1 muM) significantly decreased the release of 5-HT in the dorsal raphe and locus coeruleus to 45% and 65% of control, respectively. The release of noradrenaline was decreased in the dorsal raphe to 45% by flesinoxan, whereas no changes were seen in the release of noradrenaline in the locus coeruleus. In conclusion, the innervation of the dorsal raphe by the locus coeruleus has a slight excitatory effect on the release of 5-HT in the dorsal raphe. The dorsal raphe does not exert a direct inhibitory influence on the release of noradrenaline in the locus cocruleus. Finally, the release of noradrenaline in the dorsal raphe may be locally regulated by 5-HT1A receptors. (C) 2002 Published by Elsevier Science B.V.