EFFECTS OF 5-HT RECEPTOR AGONISTS ON DEPOLARIZATION-INDUCED [H-3] NORADRENALINE RELEASE IN RABBIT HIPPOCAMPUS AND HUMAN NEOCORTEX

1 The present study attempted to determine whether noradrenaline (NA) release in rabbit hippocampus and human neocortex is modulated by presynaptic 5-hydroxytryptamine (5-HT) receptors. 2 Slices of rabbit hippocampus and human neocortex, loaded with [H-3]-noradrenaline ([H-3]-NA) were superfused and the effects of 5-hydroxytryptamine (5-HT) receptor ligands on electrically evoked [H-3]-NA release were investigated. 3 In rabbit hippocampus, 5-HT, 5-carboxamidotryptamine (5-CT; 32 mu M) and 2-CH3-5-HT (32 mu M) increased [H-3]-NA release elicited with 360 pulses/3 Hz. Facilitation of transmitter release was not influenced by the 5-HT3 receptor antagonist, tropisetron but was prevented by the alpha(2)-adrenoceptor antagonist, rauwolscine. When autoinhibition was avoided by stimulating the tissue with 4 pulses/100 Hz (pseudo-one pulse-(POP) stimulation), 2-CH3-5-HT decreased evoked transmitter release, whereas 5-HT and 5-CT had no effect. Inhibition caused by 2-CH3-5-HT was not affected by tropisetron but counteracted by the alpha(2)-adrenoceptor ligands, clonidine and rauwolscine. Inhibition caused by clonidine was diminished in the presence of 5-CT or 2-CH3-5-HT. 4 In human neocortex, [H-3]-NA release elicited with 360 pulses/3 Hz was increased by 10 mu M 5-HT and 32 mu M 5-CT, whereas 2-CH3-5-HT was ineffective. [H-3]-NA release evoked with a modified POP stimulation (2 bursts of 4 pulses/100 Hz, 3.5 min apart) was not affected by 2-CH3-5-HT or 5-CT. 5 The present results indicate that 5-HT, 2-CH3-5-HT and 5-CT can act on presynaptic alpha(2)-autoreceptors as partial agonists (2-CH3-5-HT; in rabbit hippocampal tissue) or antagonists (5-HT and 5-CT; in tissue of rabbit hippocampus and human neocortex). Furthermore the existence of autoinhibition dictates whether these drugs cause facilitation of release, inhibition or have no effect.