Activation of 5-HT1A receptors potentiates the clonidine inhibitory effect in the locus coeruleus

• Published in: European journal of pharmacology Vol. 333; no. 2-3; pp. 159 - 162
• Main Authors: RUIZ-ORTEGA, J. A, UGEDO, L
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier 27.08.1997
• Subjects: 8-Hydroxy-2-(di-n-propylamino)tetralin - pharmacology; Adrenergic alpha-2 Receptor Antagonists; Adrenergic alpha-Agonists - pharmacology; Adrenergic alpha-Antagonists - pharmacology; Animals; Biological and medical sciences; Central nervous system; Central neurotransmission. Neuromudulation. Pathways and receptors; Chlorpromazine - pharmacology; Clonidine - pharmacology; Dopamine Antagonists - pharmacology; Dose-Response Relationship, Drug; Fundamental and applied biological sciences. Psychology; Injections, Intravenous; Isoquinolines - pharmacology; Locus Coeruleus - drug effects; Locus Coeruleus - metabolism; Male; Piperazines - pharmacology; Rats; Rats, Sprague-Dawley; Receptors, Serotonin - drug effects; Receptors, Serotonin - metabolism; Receptors, Serotonin, 5-HT1; Serotonin Receptor Agonists - pharmacology; Vertebrates: nervous system and sense organs; α2-Adrenergic receptor; Rat; Rodentia; Discharge pattern; Central nervous system; Molecular interaction; Extracellular; Neuromodulation; Mechanism; Vertebrata; Regulation(control); Mammalia; Animal; Subtype; Locus coeruleus; 5-HT1A receptor; Brain (vertebrata)
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/S0014-2999(97)01135-7

Using in vivo extracellular recordings, we have examined the effect of the application of the prototypical 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT), on the firing rate of locus coeruleus neurons. 8-OH-DPAT (1 microgram/kg, i.v.) did not modify the basal activity of the locus coeruleus but shifted to the left the dose-response curve for the clonidine induced inhibition of firing rate and reduced the corresponding ED50 by 77%. 2-[2-[4-(o-methoxyphenyl)piperazin-1-yl]ethyl]-4,4-dimethyl-1,3(2H ,4H)-isoquinolinedione (ARC 239; 75 micrograms/kg, i.v.), and chlorpromazine (75 micrograms/kg, i.v.) also shifted to the left the dose-response curve for clonidine and reduced by 38 and 46%, respectively, the ED50, while slightly increasing the basal firing rate. The results indicated that 5-HT1A receptors may modulate the responses mediated by alpha 2A-adrenoceptors in the locus coeruleus.