Abstract
The rotational behaviour induced by 5-HT agonists has been investigated in rats with lesions of the dorsal raphe' nucleus (DRN). We have previously reported that 5-methyoxy-N,N-dimethyl-tryptamine (5-MeODMT) caused dose-related contralateral rotation in rats with 5,7-dihydroxytryptamine (5,7-DHT) lesions of the DRN. Similar findings are now presented for the 5-HT1 agonists 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and 5-methoxy-3 (1,2,3,6-tetrahydropyridin-4-yl) (1H indole) (RU24969). In this model, in agreement with the behavioural studies, both agonists were shown to have a greater affinity for the 5-HT1 binding site when compared with the 5-HT2 binding site. Antagonist studies using selective 5-HT2 antagonists (ketanserin and pirenperone) at non-sedative doses failed to inhibit this behaviour. In contrast, the classical 5-HT antagonist methysergide caused significant inhibition of the rotational behaviour. These results suggest that 5-HT agonist-induced rotation in the rat is mediated via 5-HT1 receptors, probably located in the substantia nigra.
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References
Arvidsson LW, Hacksell U, Nilsson JLG, Hjorth S, Carlsson A, Lindberg P, Sanchez D, Wikstrom H (1981) 8-Hydroxy-2-(dl-N-propylamino)tetralin, a new centrally acting 5-hydroxytryptamine-receptor. J Med Chem 24:921
Blackburn TP, Cox B, Heapy CG, Lee TF, Middlemiss DN (1981) Supersensitivity of nigral serotonin receptors and rotational behaviour. Eur J Pharmacol 71:343–346
Blackburn TP, Foster GA, Heapy CG, Kemp JD (1980) Unilateral 5,7-dihydroxytryptamine lesions of the dorsal raphe' nucleus (DRN) and rat rotational behaviour. Eur J Pharmacol 67:427
Green AR, Hall JE, Rees AR (1981) A behaviour and biochemical study in rats of 5-hydroxytryptamine receptor agonists and antagonists with observations on structure-activity requirements for agonists. Br J Pharmacol 73:703–710
Hunt P, Nedelec L, Euvrard C, Boissier JR (1981) Tetrahydropyridinyl indole derivatives as serotonin analogue which may differentiate between two distinct receptor sites. 8th Int Congress of Pharmacol (IUPHAR) 1433
Konig JFR, Klippel RA (1963) The rat brain, a stereotaxic atlas. Williams and Wilkins, Baltimore
Leysen JE, Awouters F, Kennis L, Laduron PM, Vandenberk J, Janssen PAJ (1981) Receptor binding profile of R41,468. A novel antagonist at 5-HT2 receptors. Life Sci 28:1015–1022
Leysen JE, Laduron PM (1977) A serotonergic component of neuroleptic receptors (1). Arch Int Pharrmacodyn Ther 230: 337–339
Peroutka SJ, Snyder SH (1979) Multiple serotonin receptors: differential binding of [3H]-5-hydroxytryptamine [3H]-lysergic acid diethylamide and [3H]-spiroperidol. Mol Pharmacol 16:687–699
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Blackburn, T.P., Kemp, J.D., Martin, D.A. et al. Evidence that 5-HT agonist-induced rotational behaviour in the rat is mediated via 5-HT1 receptors. Psychopharmacology 83, 163–165 (1984). https://doi.org/10.1007/BF00429727
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DOI: https://doi.org/10.1007/BF00429727