Abstract
We have studied the effects of 5‐HT~1A~ and 5‐HT~7~ serotonin receptor activation in hippocampal CA3‐CA1 synaptic transmission using patch clamp on mouse brain slices. Application of either 5‐HT or 8‐OH DPAT, a mixed 5‐HT~1A~/5‐HT~7~ receptor agonist, inhibited AMPA receptor‐mediated excitatory post synaptic currents (EPSCs); this effect was mimicked by the 5‐HT~1A~ receptor agonist 8‐OH PIPAT and blocked by the 5‐HT~1A~ antagonist NAN‐190. 8‐OH DPAT increased paired‐pulse facilitation and reduced the frequency of mEPSCs, indicating a presynaptic reduction of glutamate release probability. In another group of neurons, 8‐OH DPAT enhanced EPSC amplitude but did not alter paired‐pulse facilitation, suggesting a postsynaptic action; this effect persisted in the presence of NAN‐190 and was blocked by the 5‐HT~7~ receptor antagonist SB‐269970. To confirm that EPSC enhancement was mediated by 5‐HT~7~ receptors, we used the compound LP‐44, which is considered a selective 5‐HT~7~ agonist. However, LP‐44 reduced EPSC amplitude in most cells and instead increased EPSC amplitude in a subset of neurons, similarly to 8‐OH DPAT. These effects were respectively antagonized by NAN‐190 and by SB‐269970, indicating that under our experimental condition LP‐44 behaved as a mixed agonist. 8‐OH DPAT also modulated the current evoked by exogenously applied AMPA, inducing either a reduction or an increase of amplitude in distinct neurons; these effects were respectively blocked by 5‐HT~1A~ and 5‐HT~7~ receptor antagonists, indicating that both receptors exert a postsynaptic action. Our results show that 5‐HT~1A~ receptors inhibit CA3‐CA1 synaptic transmission acting both pre‐ and postsynaptically, whereas 5‐HT~7~ receptors enhance CA3‐CA1 synaptic transmission acting exclusively at a postsynaptic site. We suggest that a selective pharmacological targeting of either subtype may be envisaged in pathological loss of hippocampal‐dependent cognitive functions. In this respect, we underline the need for new selective agonists of 5‐HT~7~ receptors. © 2011 Wiley Periodicals, Inc.