Differential autoinhibition of 5-hydroxytryptamine neurons by 5-hydroxytryptamine in the dorsal raphe nucleus.
5-Hydroxytryptamine neurons in the dorsal raphe nucleus are under autoinhibitory control by endogenous 5-hydroxytryptamine. Tonic activation of 5-hydroxytryptamine 1A autoreceptors was demonstrated in awake animals, but was inconsistently observed in anaesthetized animals and slice preparations, leading to questioning of its physiological significance. We re-evaluated autoinhibition in single-unit recordings from deeply seated 5-hydroxytryptamine neurons in slices in which endogenous 5-hydroxytryptamine bioavailability was restored by supplementing its precursor L-tryptophan. In these conditions, the application of the neutral 5-hydroxytryptamine 1A receptor antagonist WAY-100635 markedly increased 5-hydroxytryptamine neuron firing. Responses to WAY-100635 in single experiments ranged from a lack of effect to a several-fold increase in firing rate, suggesting that 5-hydroxytryptamine neurons in the dorsal raphe nucleus represent a heterogeneous population regarding their susceptibility to autoinhibition by endogenous 5-hydroxytryptamine.
Mlinar
Boris
B
Department of Preclinical and Clinical Pharmacology Mario Aiazzi-Mancini, University of Florence, Viale G. Pieraccini 6, 50139 Florence, Italy. bmlinar@unifi.it
Tatini
Francesca
F
Ballini
Chiara
C
Nencioni
Stefano
S
Della Corte
Laura
L
Corradetti
Renato
R
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D004305:Dose-Response Relationship, Drug; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D010656:Phenylephrine / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D011903:Raphe Nuclei / Q000166:cytology*; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology; D013997:Time Factors; D014364:Tryptophan / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D010879:Piperazines; D011725:Pyridines; D012702:Serotonin Antagonists; D010656:Phenylephrine; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; D014364:Tryptophan