Evidence that 5-HT2 receptor activation decreases noradrenaline release in rat hippocampus in vivo.
1. Recent electrophysiological studies have shown that 5-HT2/5-HT1C receptor agonists inhibit the electrical activity of noradrenergic neurones in the rat locus coeruleus. Here we examine the effect of various agonists and antagonists of 5-HT2/5-HT1C receptors on noradrenaline release in hippocampus of anaesthetized rats using microdialysis. 2. Subcutaneous administration of the 5-HT2/5-HT1C receptor agonist, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI: 0.2 and 0.5 mg kg-1), caused a marked decrease (50% of pre-drug levels 60 min after injection) of noradrenaline in hippocampal dialysates which was long-lasting (greater than 120 min). Noradrenaline output also decreased in response to administration of the structural analogue of DOI, 1-(2,5-dimethoxy-4-bromophenyl)-2-aminopropane (DOB: 1 mg kg-1, s.c.). 3. The effect of DOI on noradrenaline output was prevented by pretreatment with the 5-HT2/5-HT1C receptor antagonist, ritanserin (0.4 mg kg-1, s.c.). Spiperone (0.2 and 1 mg kg-1, s.c.), a 5-HT2/dopamine D2 receptor antagonist which has low affinity for 5-HT1C receptors, also antagonized the effect of DOI (0.5 mg kg-1, s.c.). Sulpiride (50 mg kg-1, s.c.), a dopamine D2 receptor antagonist did not alter the response to DOI (0.5 mg kg-1, s.c.). 4. Both the non-selective 5-HT receptor agonist, quipazine (1 mg kg-1, s.c.), and the 5-HT-releasing agent, p-chloroamphetamine (2 mg kg-1, s.c.), decreased noradrenaline release in hippocampus and these effects were antagonized by pretreatment with ritanserin (0.4 mg kg-1, s.c.).5. Our data suggest that in vivo, noradrenaline release in hippocampus is inhibited by 5-HT2 receptor activation. This effect is probably associated with a decrease in noradrenergic neuronal activity.
Done
C J
CJ
MRC Unit, Radcliffe Infirmary, Oxford.
Sharp
T
T
D004290:DOM 2,5-Dimethoxy-4-Methylamphetamine / Q000031:analogs & derivatives / Q000494:pharmacology; D000662:Amphetamines / Q000494:pharmacology; D000818:Animals; D004594:Electrophysiology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D009638:Norepinephrine / Q000378:metabolism*; D011814:Quipazine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000378:metabolism*; D016713:Ritanserin / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013134:Spiperone / Q000494:pharmacology; D013469:Sulpiride / Q000494:pharmacology; D010133:p-Chloroamphetamine / Q000494:pharmacology
D000662:Amphetamines; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; D016713:Ritanserin; D004290:DOM 2,5-Dimethoxy-4-Methylamphetamine; C003943:2,5-dimethoxy-4-bromoamphetamine; D011814:Quipazine; D013134:Spiperone; D010133:p-Chloroamphetamine; D013469:Sulpiride; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine; D009638:Norepinephrine