Serotonin-facilitated dopamine release in vivo: pharmacological characterization

The receptor specificity of serotonin (5-HT) agonist-induced facilitation of dopamine (DA) release was assessed by using in vivo microdialysis. The 5-HT receptor selective agonists RU 24969 [5-methoxy-3(1,2,3,6-tetrahydro-4-pyridinyl)-1H indole succinate], 2-methylserotonin maleate, 5-methoxytryptamine HCl, 8-hydroxy-2-(di-n-propylamino) tetralin hydrobromide and 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCl were perfused through probes located in the anterior lateral striata of chloral hydrate-anesthetized rats. The agonists increased extraneuronal levels of DA in a dose-dependent manner, suggesting receptor selectivity in the order of 5-HT1b > 5-HT4 >> 5-HT2 = 5-HT1a. Coperfusion of the 5-HT1 antagonist pindolol with RU 24969 reduced the efficacy of RU 24969. The 5-HT2 antagonist ritanserin (6-[2-[4[bis(4-fluorophenyl)methylene]-1-piperadinyl]- ethyl]-7-methyl-5H-thiazolo[3,2-a]pyrimidin-5-one) did not antagonize the effect of either 5-HT or 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCl on DA levels. MDL 72222 (3-tropanyl-3,5-dichlorobenzoate) and ICS 205930 (3-tropanyl-indole-3-carboxylate), both 5-HT3 antagonists, decreased the efficacy of 5-HT. The partial 5-HT4 antagonist ICS 205930 reduced DA released by perfusion of the 5-HT1/2/4 agonist 5-methoxytryptamine HCl. Coperfusion of antagonists with agonists indicated involvement of 5-HT1 and 5-HT3 receptors and a lack of involvement of 5-HT2 receptors in the 5-HT-induced facilitation of DA release. Determination of the role of 5-HT4 receptors will require additional work with more selective ligands.(ABSTRACT TRUNCATED AT 250 WORDS)