Repeated blockade of 5-HT7 receptors depresses glutamatergic transmission in the rat frontal cortex

The effects of the intraperitoneal administration of the 5-HT7 receptor antagonist SB 269970 were studied in the rat frontal cortex. In ex vivo slices prepared from rats receiving 14 daily doses of the drug (1.25 mg/kg) the mean frequency and the mean amplitude of glutamate-mediated, spontaneous excitatory postsynaptic currents (sEPSCs) recorded from layer II/III pyramidal neurons, were decreased. In contrast, single administration of SB 269970 affected neither the frequency nor the amplitude of sEPSCs. Treatment with SB 269970 did not affect membrane excitability of pyramidal cells. These data indicate that repeated, but not single, treatment with SB 269970 results in an attenuation of glutamatergic transmission in the frontal cortex, most likely due to a combination of pre- and postsynaptic mechanisms