Effect of BHT 920 on monoaminergic neurons of the rat brain: an electrophysiological in vivo and in vitro study.
BHT 920 was originally described as a dopamine autoreceptor agonist. In this study, the effect of this compound on the firing rate of noradrenergic locus coeruleus, serotonergic dorsal raphe and dopaminergic ventral tegmental area neurons was examined both in the anaesthetized rat and in rat brain slices. Extracellular recordings were performed in cells whose identity was determined by electrophysiological, pharmacological and histological criteria. In vivo, BHT 920 inhibited the firing of locus coeruleus neurons (ID50: 14.5 +/- 4.7 micrograms/kg, mean +/- SEM) and ventral tegmental area neurons (ID50: 7 +/- 3 micrograms/kg) at very low doses. As a comparison, the ID50 of clonidine on locus coeruleus cells was 5.5 +/- 0.6 microgram/kg and the ID50 of apomorphine on ventral tegmental area neurons was 13 +/- 3 micrograms/kg. BHT 920 also decreased the firing of dorsal raphe cells, but this effect was obtained at higher doses (ID50: 57 +/- 11 micrograms/kg). The in vitro study confirmed the results obtained in vivo. BHT 920 potently inhibited the firing of locus coeruleus cells (IC50: 71 +/- 28 nM) and was less potent than clonidine (IC50: 5.3 +/- 0.98 nM). The compound also inhibited the firing of ventral tegmental area neurons at very low concentrations (IC50: 21 +/- 3.3 nM), being more potent than apomorphine (IC50: 56 +/- 29 nM). BHT 920 only slightly decreased the firing rate of dorsal raphe neurons at 50 microM, showing that the drug has little direct effect on these cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Seutin
V
V
Department of Pharmacology, University of Liège, Sart Tilman par Liège, Belgium.
Scuvée-Moreau
J
J
Giesbers
I
I
Massotte
L
L
Dresse
A
A
D000200:Action Potentials / Q000187:drug effects; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001381:Azepines / Q000494:pharmacology*; D015306:Biogenic Monoamines / Q000502:physiology*; D001921:Brain / Q000187:drug effects*; D003000:Clonidine / Q000494:pharmacology; D004146:Dioxanes / Q000494:pharmacology; D015259:Dopamine Agents / Q000494:pharmacology*; D019329:Idazoxan; D066298:In Vitro Techniques; D008125:Locus Coeruleus / Q000187:drug effects; D008297:Male; D009474:Neurons / Q000187:drug effects*; D011903:Raphe Nuclei / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D013469:Sulpiride / Q000494:pharmacology; D013681:Tegmentum Mesencephali / Q000187:drug effects
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D001381:Azepines; D015306:Biogenic Monoamines; D004146:Dioxanes; D015259:Dopamine Agents; C024763:talipexole; D013469:Sulpiride; D003000:Clonidine; D001058:Apomorphine; D019329:Idazoxan