Activation of 5-HT1A receptors potentiates the clonidine inhibitory effect in the locus coeruleus.
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.
Ruiz-Ortega
J A
JA
Departamento de Farmacología, Universidad del País Vasco, Leioa, Vizcaya, Spain.
Ugedo
L
L
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D058669:Adrenergic alpha-2 Receptor Antagonists; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D002746:Chlorpromazine / Q000494:pharmacology; D003000:Clonidine / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007275:Injections, Intravenous; D007546:Isoquinolines / Q000494:pharmacology; D008125:Locus Coeruleus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000378:metabolism; D044263:Receptors, Serotonin, 5-HT1; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*
D058669:Adrenergic alpha-2 Receptor Antagonists; D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D018492:Dopamine Antagonists; D007546:Isoquinolines; D010879:Piperazines; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D017366:Serotonin Receptor Agonists; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; C032994:AR-C239; D003000:Clonidine; D002746:Chlorpromazine