Effects of 5‐HT receptor agonists on depolarization‐induced [3H]‐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 [3H]‐noradrenaline ([3H]‐NA) were superfused and the effects of 5‐hydroxytryptamine (5‐HT) receptor ligands on electrically evoked [3H]‐NA release were investigated 3 In rabbit hippocampus, 5‐HT, 5‐carboxamidotryptamine (5‐CT; 32 μm) and 2‐CH3‐5‐HT (32 μm) increased [3H]‐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 α2‐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 α2‐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, [3H]‐NA release elicited with 360 pulses/3 Hz was increased by 10 μm 5‐HT and 32 μm 5‐CT, whereas 2‐CH3‐5‐HT was ineffective. [3H]‐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 a2‐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.