Premium
Effect of the selective noradrenergic reuptake inhibitor reboxetine on the firing activity of noradrenaline and serotonin neurons
Author(s) -
Szabo Steven T.,
Blier Pierre
Publication year - 2001
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1046/j.0953-816x.2001.01583.x
Subject(s) - reboxetine , chemistry , agonist , locus coeruleus , reuptake , reuptake inhibitor , dorsal raphe nucleus , serotonin , pharmacology , endocrinology , medicine , serotonergic , receptor , central nervous system , biochemistry
Reboxetine is a non‐tricyclic antidepressant with selective noradrenergic (NA) reuptake‐blocking effects. The effects of acute and sustained administration of reboxetine, on the firing activity of locus coeruleus NA neurons and dorsal raphe 5‐HT neurons, were assessed using in vivo extracellular unitary recording in rats anaesthetized with chloral hydrate. Reboxetine (0.1–1.25 mg/kg, i.v.) dose‐dependently decreased the firing activity of NA neurons (ED 50 = 480 ± 14 µg/kg). A 2‐day treatment with reboxetine at 1.25, 2.5, 5, or 10 mg/kg per day (using osmotic minipumps implanted subcutaneously) produced significant decreases of 52%, 68%, 81%, and 83%, respectively, of NA firing activity. When the reboxetine treatment (2.5 mg/kg per day) duration was prolonged to 7 days, a 66% decrease in NA firing activity was observed which further decreased to 80% after 21 days of treatment. In contrast, 5‐HT neuron firing rate remained unaltered following short‐ and long‐term reboxetine treatments. The suppressant effect of the α 2 ‐adrenoceptor agonist clonidine on the firing activity of NA neurons was unchanged in long‐term reboxetine‐treated rats, but its effect on the firing activity of 5‐HT neurons was blunted. The enhancement of NA firing activity by the 5‐HT 1A agonist 8‐OH‐DPAT was abolished in long‐term reboxetine‐treated rats, whereas, the inhibitory effect of the 5‐HT 2 agonist DOI was attenuated by about three‐fold. In conclusion, sustained NA reuptake blockade by reboxetine lead to profound alterations in the function of NA neurons and of 5‐HT receptors modulating their firing activity.