Prolonged administration of imipramine and (+)-oxaprotiline, but not citalopram, results in sensitization of the rat hippocampal CA1 neurons to serotonin ex vivo.

Prolonged (14 days, twice daily), but not acute, application of imipramine and (+)-oxaprotiline (10 mg/kg) induced sensitization of hippocampal CA1 neurons to the inhibitory effect of 5-hydroxytryptamine (5-HT), as studied ex vivo in the rat hippocampal slice preparation. Attenuation of the population spike, recorded in the CA1 pyramidal cell layer in response to stimulation of the Schaffer collateral-commisural pathway, was used to asses the sensitivity of neurons to 5-HT. Prolonged and acute administration of the selective 5-HT reuptake blocker citalopram did not change the responsiveness of hippocampal neurons to 5-HT. Since imipramine and (+)-oxaprotiline share the inhibitory effect on the norepinephrine reuptake, our results may indicate that long-term alterations in the noradrenergic system lead to modifications in postsynaptic serotonergic receptors.