Perforant path inhibition by noradrenaline and serotonin JN-00217-2005.R1 Inhibition of perforant path input to the CA1 region by serotonin and noradrenaline

Bath applied monoamines dopamine (DA), serotonin (5-HT), and noradrenaline (NE) strongly suppress the perforant path (PP) input to CA1 hippocampal region with very little effect on the Schaffer collaterals (SC) input (Otmakhova and Lisman, 2000). The effect of DA action on PP field EPSP (fEPSP) has been characterized in detail (Otmakhova and Lisman, 1999), but relatively little is known about the NE and 5-HT effects. Here we show that the maximal inhibition of the PP fEPSP by NE is ~55 % whereas 5-HT inhibition is weaker (~35 %). The half-maximal inhibitory concentration of both 5-HT and NE is ~1 μM. Neither NE nor 5-HT affected paired-pulse facilitation, suggesting that the effect is not presynaptic. This is in contrast to DA, which does have a presynaptic effect. The NE effect was blocked by α2 antagonists, whereas the α1 antagonist corynanthine and β-antagonist propranolol were ineffective. The effect of 5-HT was mimicked by the agonist, 5-carboxamidotryptamine maleate (5-CT) and not affected by adrenergic and dopaminergic antagonists. In order to determine the 5-HT receptors involved, we tested a number of 5-HT antagonists but none produced a complete suppression of the 5-HT effect. Of these, only the 5-HT7 and 5-HT2 antagonists produced weak but significant inhibition of 5-HT effect. We conclude that NE inhibits the PP fEPSP via postsynaptic action on α2-adrenoceptors and that 5-HT7, 5-HT2, and some other receptor may be involved in 5-HT action in PP.