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

• Published in: The Journal of neuroscience Vol. 22; no. 17; pp. 7509 - 7517
• Main Authors: Hasuo, Hiroshi, Matsuoka, Toshimasa, Akasu, Takashi
• Format: Journal Article
• Language: English
• Published: United States Soc Neuroscience 01-09-2002; Society for Neuroscience
• Subjects: Animals; Cyclic AMP-Dependent Protein Kinases - antagonists & inhibitors; Enzyme Inhibitors - pharmacology; Excitatory Postsynaptic Potentials - drug effects; Excitatory Postsynaptic Potentials - physiology; GABA Antagonists - pharmacology; GABA-A Receptor Antagonists; GABA-B Receptor Antagonists; Glutamic Acid - pharmacology; GTP-Binding Proteins - drug effects; GTP-Binding Proteins - metabolism; In Vitro Techniques; Male; Neurons - drug effects; Neurons - metabolism; Presynaptic Terminals - metabolism; Protein Kinase C - antagonists & inhibitors; Protein Kinase C - metabolism; Rats; Rats, Wistar; Receptor, Serotonin, 5-HT2A; Receptors, Serotonin - metabolism; Septal Nuclei - cytology; Septal Nuclei - drug effects; Septal Nuclei - metabolism; Serotonin - pharmacology; Serotonin Antagonists - pharmacology; Serotonin Receptor Agonists - pharmacology; Synaptic Transmission - drug effects; Synaptic Transmission - physiology; Virulence Factors, Bordetella - pharmacology
• ISSN: 0270-6474; 1529-2401
• DOI: 10.1523/jneurosci.22-17-07509.2002

Effects of 5-hydroxytryptamine (5-HT) on EPSPs and EPSCs in the rat dorsolateral septal nucleus (DLSN) were examined in the presence of GABA(A) and GABA(B) receptor antagonists. Bath application of 5-HT (10 microm) for 5-10 min increased the amplitude of the EPSP and EPSC. (+/-)-8-hydroxy-2-(di-N-propylamino)tetralin hydrobromide (10 microm), an agonist for 5-HT1A and 5-HT7 receptors, did not facilitate the EPSP. alpha-Methyl-5-HT (10 microm), a 5-HT2 receptor agonist, increased the amplitude of the EPSC. Alpha-methyl-5-(2-thienylmethoxy)-1H-indole-3-ethanamine (10 microm) and 6-chloro-2-(1-piperazinyl)pyrazine (10 microm), selective 5-HT2B and 5-HT2C receptor agonists, respectively, had no effect on the EPSP. The 5-HT-induced facilitation of the EPSP was blocked by ketanserin (10 microm), a 5-HT2A/2C receptor antagonist. However, N-desmethylclozapine (10 microm), a selective 5-HT2C receptor antagonist, did not block the facilitation of the EPSP induced by alpha-methyl-5-HT. The inward current evoked by exogenous glutamate was unaffected by 5-HT. 5-HT (10 microm) and alpha-methyl-5-HT (10 microm) 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 alpha-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 by N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide (10 microm), a protein kinase A inhibitor. Phorbol 12,13-dibutyrate (3 microm) 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-HT2A receptors that link with PKC in rat DLSN neurons.