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Effects of the antidepressant compound nefazodone on central monoaminergic neuronal discharge in rats
Author(s) -
Vandermaelen Cam P.,
Braselton John P.
Publication year - 1992
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.430250309
Subject(s) - chemistry , locus coeruleus , ritanserin , carbenoxolone , chloral hydrate , monoaminergic , pharmacology , nefazodone , dorsal raphe nucleus , prazosin , medicine , endocrinology , serotonergic , antagonist , serotonin , central nervous system , receptor , gap junction , biochemistry , intracellular , fluoxetine
The effects of i.v. administration of the antidepressant compound nefazodone were assessed on the firing rates of spontaneously active noradrenergic neurons in the locus coeruleus (LC), serotonergic neurons in the dorsal raphe (DR), and dopaminergic neurons in the substantia nigra (SN) of chloral hydrate anesthetized male albino adult rats, utilizing extracellular single‐unit recording methods. Nefazodone, tested in doses of 0.1–10.0 mg/kg, had variable effects on LC neurons, but the predominant effect was a mild excitation of firing (ED 25 = 1.953 mg/kg). This may in part be caused by the 5‐HT 2 antagonist properties of the compound, since ritanserin also produced a mild excitation of LC neurons. By comparison, desipramine very reliably inhibited LC neurons (ED 50 = 0.333 mg/kg, i.v.). For DR neurons, i.v. nefazodone (0.1–3.2 mg/kg) produced variable effects, with inhibition being the most common (63% of cases tested). The ED 25 for inhibition was 1.230 mg/kg, and in no case was inhibition of 50% or greater observed. By comparison, clomipramine very reliably inhibited DR neurons (ED 50 = 0.501 mg/kg, i.v.). For SN neurons, the effects of i.v. nefazodone were also variable, with no consistent effects observed. These results indicate that acute nefazodone produces relatively weak effects on monoaminergic neuronal impulse flow in anesthetized rats, and suggest that major modifications of monoaminergic neuronal impulse flow probably do not play an important role in any neuroadaptive changes that may contribute to the clinical antidepressant actions of nefazodone.