caa a22 4500 469077832 CHVBK 20180323132940.0 cr unu---uuuuu 170328e19920701xx s 000 0 eng 10.1007/BF00167564 doi (NATIONALLICENCE)springer-10.1007/BF00167564 The influence of serotoninergic drugs on dopaminergic neurotransmission in rat substantia nigra, striatum and limbic forebrain in vivo [Elektronische Daten] [Hans Nissbrandt, Nicholas Waters, Stephan Hjorth] Summary: The effects of serotoninergic drugs on dopaminergic neurotransmission in the substantia nigra, the striatum and the limbic forebrain of rat have been investigated. The accumulation of 3-methoxytyramine (3-MT) following inhibition of monoamine oxidase with pargyline was used as an indirect measure of dopamine (DA) activity in vivo. The effects of the following serotoninergic drugs were tested: the 5-HT1A receptor agonist 8-OH-DPAT, the 5-HT1B receptor agonist trifluoromethyl-phenylpiperazine (TFMPP), CGS 12066B and RU 24969, the 5-HT1A/1B antagonist (±)pindolol, the 5-HT2/1C receptor antagonist ritanserin, the 5-HT2/1C receptor agonist DL-1-(2,5-dimethoxy-4-iodo-phenyl)-2-aminopropane (DOI), the 5-HT3 receptor antagonist BRL 43 694, the unselective 5-HT1 receptor antagonist methiothepin, and carbidopa+L-5-hydroxytryptophan (L5-HTP) to achieve a general, unselective stimulation of multiple 5-HT receptors. In the substantia nigra, carbidopa + 5-HTP treatment increased the 3-MT accumulation by 26% and decreased the DA concentration to 67% of controls, tentatively suggesting a 5-HTP-induced displacement of nigral DA. A minor, non dose-related reduction in nigral 3-MT was seen after the 5-HT1A receptor agonist 8-OH-DPAT. None of the other serotonin receptor acting drugs induced any pronounced effect on the nigral 3-MT accumulation. Taken together, the findings provide little support for the idea that one single 5-HT1 receptor subtype serves a modulatory function on DA activity in the substantia nigra. In the striatum and the limbic forebrain, trifluoromethylphenylpiperazine dose-dependently increased the 3-MT accumulation to maximally 200%-220% of controls. In the limbic forebrain also the highest dose of RU 24 969 (15 mg/kg) increased the 3-MT accumulation (78%), whereas in the striatum the lowest does of the drug (1.5 mg/kg) decreased it by 30%. The trifluoromethylphenylpiperazine-induced stimulation of 3-MT accumulation was not blocked by ritanserin. In the limbic forebrain, also DL-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane and carbidopa+Lr5-HTP treatment increased the 3-MT concentrations to 120% and 150% of controls, respectively. Paradoxically, methiothepin also induced an increase of the 3-MT accumulation in these brain regions, probably due to its DA receptor antagonism. None of the other serotoninergic drugs induced any pronounced effects on the 3-MT accumulation in these brain parts. The results may overall support the hypothesis that 5-HT1 does modulate the DA activity in the striatum and limbic forebrain, tentatively via 5-HT1B receptors in the striatum and 5-HT1B and 5-HT2 or 5-HT1C receptors in the limbic forebrain. It may be speculated therefore, that clinical application of 5-HT1 receptor-modulating drugs to influence central dopaminergic activity might be of therapeutical benefit, for example, in motor disorders like Parkinson's disease. Springer-Verlag, 1992 Substantia nigra nationallicence Striatum nationallicence Limbic forebrain nationallicence Dopamine release nationallicence Serotonin receptor-mediated regulation nationallicence Nissbrandt Hans Department of Pharmacology, University of Göteborg, P.O. Box 33031, S-400 33, Göteborg, Sweden aut Waters Nicholas Department of Pharmacology, University of Göteborg, P.O. Box 33031, S-400 33, Göteborg, Sweden aut Hjorth Stephan Department of Pharmacology, University of Göteborg, P.O. Box 33031, S-400 33, Göteborg, Sweden aut Naunyn-Schmiedeberg's Archives of Pharmacology Springer-Verlag 346/1(1992-07-01), 12-19 0028-1298 346:1<12 1992 346 210 https://doi.org/10.1007/BF00167564 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF00167564 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Nissbrandt Hans Department of Pharmacology, University of Göteborg, P.O. Box 33031, S-400 33, Göteborg, Sweden aut NATIONALLICENCE 700 1- Waters Nicholas Department of Pharmacology, University of Göteborg, P.O. Box 33031, S-400 33, Göteborg, Sweden aut NATIONALLICENCE 700 1- Hjorth Stephan Department of Pharmacology, University of Göteborg, P.O. Box 33031, S-400 33, Göteborg, Sweden aut NATIONALLICENCE 773 0- Naunyn-Schmiedeberg's Archives of Pharmacology Springer-Verlag 346/1(1992-07-01), 12-19 0028-1298 346:1<12 1992 346 210 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer