Autoregulatory properties of dorsal raphe 5-HT neurons: possible role of electrotonic coupling and 5-HT1D receptors in the rat brain.
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.
Piñeyro
G
G
Department of Psychiatry, McGill University, Montreal, Quebec, Canada.
de Montigny
C
C
Weiss
M
M
Blier
P
P
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D003712:Dendrites / Q000187:drug effects / Q000502:physiology; D004558:Electric Stimulation; D004594:Electrophysiology; D005110:Extracellular Space / Q000187:drug effects / Q000502:physiology; D007211:Indoles / Q000494:pharmacology; D008297:Male; D008803:Mianserin / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011903:Raphe Nuclei / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D012701:Serotonin / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013569:Synapses / Q000187:drug effects / Q000502:physiology
D007211:Indoles; D010879:Piperazines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D008803:Mianserin; C018406:1-(3-trifluoromethylphenyl)piperazine; C025145:5-methoxy 3-(1,2,3,6-tetrahydro-4-pyridinyl)1H indole; D012701:Serotonin; D011433:Propranolol