5-HYDROXYTRYPTAMINE-3 RECEPTORS MODULATE SYNAPTIC ACTIVITY IN THE RAT NUCLEUS-TRACTUS-SOLITARIUS INVITRO

Whole-cell patch clamp recordings were made from neurons in the rat nucleus tractus solitarius (NTS) in transverse brainstem slices. 5-Hydroxytryptamine (5-HT, 100-mu-M) and the selective 5-HT3 receptor agonist 2-methyl-5-HT (2-CH3-5-HT, 100-mu-M) depolarized 86% of NTS neurons at resting membrane potential (V(m)). This response was resistant to tetrodotoxin (TTX) and Co2+ application. In addition, 2-CH3-5-HT (500 nM-100-mu-M) increased the amplitude and frequency of both excitatory and inhibitory spontaneous synaptic potentials. This effect was also TTX-resistant, but was abolished by Co2+. The effects of 2-CH3-5-HT on EPSPs and IPSPs evoked by electrical stimulation of the tractus solitarius (TS) were analyzed separately in the presence of bicuculline or 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), respectively. Concentrations of 2-CH3-5-HT between 500 nM and 1-mu-M decreased the amplitude of evoked EPSPs and IPSPs with similar potency. The selective 5-HT3 receptor antagonists ICS 205-930 (10 nM) and MDL 72222 (10-mu-M) reversibly blocked the effects of 2-CH3-5-HT at all doses examined. It is concluded that 5-HT3 receptors can mediate both pre- and postsynaptic responses in the NTS.