The effects of 5-hydroxytryptamine (5-HT) on neuronal excitability, evaluated as depolarisation-induced firing rate, and on amino acid release, measured as electrically-evoked [3H]GABA and [3H]-D-aspartate efflux, were investigated in rat primary cortical neuronal cultures. 5-HT displayed a concentration-dependent, bimodal effect on neuronal excitability: at 3-10 µM it increased excitability through 5-HT2A receptors, and was blocked by the selective 5-HT2A antagonist MDL 100907, whereas at 30-100 µM it reduced excitability through 5-HT1A receptors, and was, in turn, blocked by the selective 5-HT1A antagonist WAY 100135. The electrically-evoked [3H]GABA efflux was concentration-dependently inhibited by 5-HT (pEC50 = 4.74) and such inhibition was prevented by WAY 100135, but not by Gr 55562, a selective 5-HT1D/B receptor antagonist Conversely, 5-HT concentration-dependently increased stimulus-evoked [3H]D-aspartate efflux (pEC50 = 4.71). The increase was facilitated by methiothepin and was reversed into inhibition by ICS 205930, a selective 5-HT3 receptor antagonist. In the presence of ICS 205930, the inhibition induced by 5-HT was prevented by the selective 5-HT1D/B receptor antagonist Gr 55562, but not by WAY 100135. These findings suggest that 5-HT inhibits GABA release through 5-HT1A receptors and exerts a dual modulation on glutamate release, mostly facilitatory (through 5-HT3 receptors) but also inhibitory (through 5-HT1D/B receptors), leading to a prevalently positive modulation of the excitatory signal by amino acid neurotransmitter containing neurons.
Serotonin modulation of cell excitability and of [3-H]GABA and [3-H]D-aspartate efflux in primary cultures of rat cortical neurons
BIANCHI, Clementina;MARANI, Luca;BARBIERI, Mario;NAZZARO, Cristiano;BEANI, Lorenzo;SINISCALCHI, Anna
2007
Abstract
The effects of 5-hydroxytryptamine (5-HT) on neuronal excitability, evaluated as depolarisation-induced firing rate, and on amino acid release, measured as electrically-evoked [3H]GABA and [3H]-D-aspartate efflux, were investigated in rat primary cortical neuronal cultures. 5-HT displayed a concentration-dependent, bimodal effect on neuronal excitability: at 3-10 µM it increased excitability through 5-HT2A receptors, and was blocked by the selective 5-HT2A antagonist MDL 100907, whereas at 30-100 µM it reduced excitability through 5-HT1A receptors, and was, in turn, blocked by the selective 5-HT1A antagonist WAY 100135. The electrically-evoked [3H]GABA efflux was concentration-dependently inhibited by 5-HT (pEC50 = 4.74) and such inhibition was prevented by WAY 100135, but not by Gr 55562, a selective 5-HT1D/B receptor antagonist Conversely, 5-HT concentration-dependently increased stimulus-evoked [3H]D-aspartate efflux (pEC50 = 4.71). The increase was facilitated by methiothepin and was reversed into inhibition by ICS 205930, a selective 5-HT3 receptor antagonist. In the presence of ICS 205930, the inhibition induced by 5-HT was prevented by the selective 5-HT1D/B receptor antagonist Gr 55562, but not by WAY 100135. These findings suggest that 5-HT inhibits GABA release through 5-HT1A receptors and exerts a dual modulation on glutamate release, mostly facilitatory (through 5-HT3 receptors) but also inhibitory (through 5-HT1D/B receptors), leading to a prevalently positive modulation of the excitatory signal by amino acid neurotransmitter containing neurons.I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
