Adaptive changes in the reactivity of 5-HT1A and 5-HT2 receptors induced in rat frontal cortex by repeated imipramine and citalopram

Using extracellular ex vivo recording we studied changes in the reactivity of rat frontal cortical neurons to the 5-HT1A, 5-HT2 and 5-HT4 receptor agonists (+/-)-2-dipropyloamino-8-hydroxy-1,2,3,4-tetrahydronaphtalene hydrobromide (8-OH-DPAT), (+/-)-2,5-dimethoxy-4-iodoamphetamine hydrochloride (DOI) and zacopride, respectively, induced by a repeated treatment with imipramine or citalopram. Rats were treated with imipramine or citalopram for 14 days (10 mg/kg p.o.) twice daily. Frontal cortical slices were prepared 2 days after the last drug administration. Spontaneous epileptiform discharges were induced in slices by perfusion with a medium devoid of Mg2+ ions and with added picrotoxin (30 muM). While the application of 2 muM 8-OH-DPAT resulted in a reversible decrease of the discharge frequency, in the presence of DOI (1 muM) or zacopride (5 muM), the discharge frequency was increased. Both repeated imipramine and citalopram enhanced the effect of the activation of 5-HT1A receptor and attenuated the effect related to 5-HT2 receptor activation, while the effect of the activation of 5-HT4 receptor remained unchanged. Moreover, imipramine, but not citalopram, induced a reduction of epileptiforrn discharge frequency and an increase of the time of occurrence of epileptiform activity. These data indicate that antidepressants enhance the 5-HT-mediated inhibition in neuronal circuitry of the frontal cortex.