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Effects of 5-hydroxytryptamine (5-HT) on EPSPs and EPSCs in the rat dorsolateral septal nucleus (DLSN) were examined in the presence of GABAA and GABAB receptor antagonists. Bath application of 5-HT (10 μm) for 5–10 min increased the amplitude of the EPSP and EPSC. (±)-8-Hydroxy-2-(di-N-propylamino)tetralin hydrobromide (10 μm), an agonist for 5-HT1A and 5-HT7 receptors, did not facilitate the EPSP. α-Methyl-5-HT (10 μm), a 5-HT2 receptor agonist, increased the amplitude of the EPSC. α-Methyl-5-(2-thienylmethoxy)-1H-indole-3-ethanamine (10 μm) and 6-chloro-2-(1-piperazinyl)pyrazine (10 μm), selective 5-HT2B and 5-HT2Creceptor agonists, respectively, had no effect on the EPSP. The 5-HT-induced facilitation of the EPSP was blocked by ketanserin (10 μm), a 5-HT2A/2C receptor antagonist. However, N-desmethylclozapine (10 μm), a selective 5-HT2C receptor antagonist, did not block the facilitation of the EPSP induced by α-methyl-5-HT. The inward current evoked by exogenous glutamate was unaffected by 5-HT. 5-HT (10 μm) and α-methyl-5-HT (10 μm) increased the frequency of miniature EPSPs (mEPSPs) without changing the mEPSP amplitude. The ratio of the paired pulse facilitation was significantly decreased by 5-HT and α-methyl-5-HT. The 5-HT-induced facilitation of the EPSP was blocked by calphostin C (100 nm), a specific protein kinase C (PKC) inhibitor, but not byN-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide (10 μm), a protein kinase A inhibitor. Phorbol 12,13-dibutyrate (3 μm) mimicked the facilitatory effects of 5-HT. These results suggest that 5-HT enhances the EPSP by increasing the release of glutamate via presynaptic 5-HT2Areceptors that link with PKC in rat DLSN neurons.

the journal of neuroscience/the journal of neuroscience

Activation of Presynaptic 5-Hydroxytryptamine 2A Receptors Facilitates Excitatory Synaptic Transmission via Protein Kinase C in the Dorsolateral Septal Nucleus