EVIDENCE THAT 5-HT2 RECEPTOR ACTIVATION DECREASES NORADRENALINE RELEASE IN RAT HIPPOCAMPUS INVIVO

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 (> 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.