5-hydroxytryptamine₂ receptor facilitates GABAergic neurotransmission in rat hippocampus

5-Hydroxytryptamine (5-HT; serotonin) administration enhances GABAergic synaptic activity recorded in pyramidal neurons of the CA1 region of hippocampus. Previous studies have attributed this effect to the activation of HT-5₃ receptors located on GABAergic interneurons. During unrelated experiments, we noticed that under our recording conditions, 5-HT can still increase GABAergic synaptic activity after the complete blockade of 5-HT₃ receptors. This indicated the involvement of an additional 5-HT receptor subtype. Therefore, we reinvestigated the effects of 5-HT on GABAergic synaptic activity recorded in pyramidal cells of the CA1 region. The ability of 5-HT to increase GABAergic synaptic activity in the presence of 5-HT₃ receptor blockade was mimicked by the selective 5-HT₂ agonist (±)-1-(2,5- dimethoxy-4-iodophenyl)-2-aminopropane and blocked by the selective 5-HT₂ antagonist ketanserin. This indicated that the additional 5-HT receptor belongs to 5-HT₂ receptor family. 5-HT₂ receptor activation resulted in an increase in the frequency of spontaneous inhibitory postsynaptic currents as well as a shift in their amplitude distribution toward larger sizes. These effects were absent in the presence of tetrodotoxin. We interpret these results to indicate that 5-HT₂ receptors activate GABAergic interneurons in the slice, leading to an increase in GABAergic synaptic activity onto pyramidal cells of the CA1 region.