8-OH-DPAT-induced release of hippocampal noradrenaline in vivo: evidence for a role of both 5-HT1A and dopamine D1 receptors.
Here we investigate the effects of the novel selective 5-HT1A receptor antagonist, N-[2-[4-(2 methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl cyclo-hexanecarboxamide (WAY 100635), and the dopamine D1 receptor antagonist, R-(+)-8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepin++ +-7-ol (SCH 23390), on the increase in extracellular noradrenaline in rat hippocampus induced by the 5-HT1A receptor agonist, 8-hydroxy-2-(di-N-propylamino)tetralin (8-OH-DPAT). 8-OH-DPAT (0.1 and 1 mg/kg s.c.) caused a dose-related increase in extracellular noradrenaline. WAY 100635 (0.3 and 1 mg/kg s.c.) did not block the release of noradrenaline induced by the higher dose of 8-OH-DPAT (1 mg/kg s.c.) but abolished the response to the lower dose (0.1 mg/kg s.c.). When administered alone, WAY 100635 (0.3 and 1 mg/kg s.c.) had no effect on extracellular noradrenaline. The postsynaptically mediated 5-HT behavioural syndrome induced by the higher dose of 8-OH-DPAT, in contrast to the increase in noradrenaline, was completely blocked by WAY 100635 (0.3 mg/kg s.c.). Finally, the noradrenaline response to 8-OH-DPAT (0.1 mg/kg s.c.) was blocked by SCH 23390 (0.5 mg/kg s.c.). Our data confirm that noradrenaline can be released by activation of 5-HT1A receptors but show that these receptors are not tonically activated, and may be more sensitive to stimulation than classical postsynaptic 5-HT1a receptors. A role for the dopamine D1 receptor in the noradrenaline response to 8-OH-DPAT is also suggested.
Hajós-Korcsok
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University Department of Clinical Pharmacology, Radcliffe Infirmary, Oxford, UK.
Sharp
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D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001552:Benzazepines / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D010879:Piperazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors / Q000502:physiology*; D011985:Receptors, Serotonin / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology
D001552:Benzazepines; D018492:Dopamine Antagonists; D010879:Piperazines; D011725:Pyridines; D017447:Receptors, Dopamine D1; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D009638:Norepinephrine