ACTIONS OF 5-HYDROXYTRYPTAMINE ON NEURONS OF THE RAT CINGULATE CORTEX

1. Intracellular recordings were made from layer V pyramidal neurons in slices of rat cingulate cortex. Electrodes contained potassium methylsulphate and biocytin for subsequent histology. 2. Synaptic potentials were separated pharmacologically with DL-2-amino-5-phosphonovaleric acid (APV), 6-cyano-7-nitro-quinoxaline-2,3-dione (CNQX), bicuculline, and 2-hydroxysaclofen into components mediated, respectively, by N-methyl-D-aspartate (NMDA) type excitatory amino acid, non-NMDA type excitatory amino acid, gamma-aminobutyric acid (GABA(A)), and GABA(B) receptors. Components mediated at excitatory amino acid, GABA(A) and GABA(B) receptors reversed polarity at -11, -76, and -108 mV, respectively. 3. When synaptic potentials were evoked by stimulation to the subcortical white matter, 5-hydroxytryptamine (5-HT; 1-100 muM) reversibly reduced the amplitude of NMDA, non-NMDA, GABA(A), and GABA(B) components. Selective agonists and antagonists were used to show that this resulted from activation of 5-HT1B receptors. 4. When synaptic potentials were evoked by stimulation within layer V, 5-HT reduced the amplitude only of the NMDA and non-NMDA components but did not affect the GABA(A) and GABA(B) components. 5-HT did not change the amplitude of depolarizations evoked by direct application of glutamate. 5. It is concluded that 5-HT presynaptically inhibits the release of excitatory amino acids at synapses onto prefrontal pyramidal neurons and at synapses onto local feed-forward inhibitory interneurons. 6. 5-HT also hyperpolarized, depolarized, or did not change the membrane potential. The hyperpolarization involved 5-HT1A receptors and resulted from potassium conductance increase. The depolarization involved 5-HT2 receptors and resulted from potassium conductance decrease.