Autoregulatory properties of dorsal raphe 5-HT neurons: possible role of electrotonic coupling and 5-HT1D receptors in the rat brain.

Abstract

In the present study, the hypothesis that somatodendritic availability of 5-hydroxytryptamine (5-HT) could be regulated independently of the firing activity of dorsal raphe 5-HT neurons was tested. The 5-HT pathway was electrically stimulated at the level of the ventromedial tegmentum and the ensuing action potentials, recorded in the dorsal raphe, met all criteria for antidromic invasion of 5-HT neurons. The latency of antidromic spikes was current-dependent and the changes in latency were of quantal nature. This observation suggests an electrotonic coupling between 5-HT neurons. Stimulation of the ventromedial tegmentum also induced a decrease in the probability of firing of 5-HT neurons. This reduction in 5-HT neuron firing activity is a 5-HT-mediated response, due to an increased bioavailability of the neurotransmitter in the biophase of somatodendritic 5-HT1A autoreceptors. The intravenous administration of the 5-HT1 agonists TFMPP and RU 24969 reduced the duration of suppression of firing induced by the 5-HT-pathway stimulation, without altering the spontaneous firing rate of 5-HT neurons. The effect of TFMPP and RU 24969 on duration of suppression was blocked by (+-)mianserin, a drug with high affinity for the rat 5-HT1D, but not 5-HT1B, receptors. On the other hand, (-)propranolol, a mixed 5-HT antagonist also blocked the effect of TFMPP. However, the selective 5-HT1A antagonist (+)WAY 100135 did not alter the effect of TFMPP. These results, in keeping with previous anatomical studies, suggest the existence of electrotonic coupling of 5-HT neurons and indicate that 5-HT release in the rat dorsal raphe nucleus may be controlled independently of firing-regulating 5-HT1A autoreceptors. They also suggest that 5-HT1D receptors may play a role in this regulatory function of 5-HT neurons.