Stimulatory effect of harmane and other beta-carbolines on locus coeruleus neurons in anaesthetized rats.
Harmane, harmaline and norharmane are beta-carboline related compounds which have been proposed to be endogenous ligands for imidazoline receptors. The effect of these compounds on the activity of locus coeruleus (LC) neurons was studied by extracellular recordings techniques. Intracerebroventricular administration of harmane and harmaline increased the firing rate of LC neurons. Systemic administration of efaroxan, a mixed alpha(2)-adrenoceptor/I(1)-imidazoline antagonist or vagotomy failed to modify the harmane effect. Furthermore, local applications of harmane and harmaline increased the firing rate of LC neurons in a dose-related manner. Finally, intravenous administration of norharmane also increased the activity of LC neurons. Our results demonstrate that beta-carbolines stimulate LC neuron activity and indicate that this stimulation occurs directly in the LC by a mechanism independent of I(1)- and I(2)-imidazoline receptors.
Ruiz-Durántez
E
E
Department of Pharmacology, Faculty of Medicine, University of the Basque Country, E-48940 Leioa, Vizcaya, Spain.
Ruiz-Ortega JA
Pineda
J
J
Ugedo
L
L
D000758:Anesthesia; D000818:Animals; D002243:Carbolines / Q000494:pharmacology; D004594:Electrophysiology; D006246:Harmaline / Q000494:pharmacology; D006247:Harmine / Q000031:analogs & derivatives / Q000494:pharmacology*; D054755:Imidazoline Receptors; D008125:Locus Coeruleus / Q000166:cytology* / Q000187:drug effects*; D008297:Male; D009474:Neurons / Q000187:drug effects*; D009498:Neurotoxins / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011955:Receptors, Drug / Q000502:physiology; D014628:Vagotomy
D002243:Carbolines; D054755:Imidazoline Receptors; D009498:Neurotoxins; D011955:Receptors, Drug; D006247:Harmine; C005010:harman; C010262:norharman; D006246:Harmaline