Involvement of 5-HT1A receptors in the anxiolytic action of S 14671 in the pigeon conflict test. 1995

R Schreiber, and M Brocco, and B L de Ladonchamps, and M J Millan
Department of Psychopharmacology, Centre de Recherches de Croissy, France.

In the pigeon conflict test of anxiety, the novel, high efficacy 5-HT1A receptor ligand, S 14671, very potently [minimal effective dose (MED): 0.0025 mg/kg, IM] and markedly (maximal percentage increase relative to control: 17232%) increased punished responding. In analogy, its structural analogue, the 5-HT1A receptor agonist, S 14506, equipotently, though less markedly, augmented punished responding (MED: 0.0025 mg/kg; maximal effect: 5557%). In contrast, the arylpiperazine 5-HT1A receptor agonists, LY 165,163 and tandospirone, increased punished responding only at higher doses (MED: 0.16 and 0.63 mg/kg, respectively), and also with a lesser maximal effect (2065% and 3695%, respectively). Although S 14671 and S 14506 showed a 16-fold separation between doses, increasing punished and decreasing unpunished responding, respectively, this separation was only fourfold for LY 165,163 and tandospirone. The anticonflict activity of S 14671 (0.01 mg/kg) was significantly antagonised by the 5-HT1A receptor antagonist, (-)-alprenolol (10 mg/kg), but not by combined treatment with the selective beta 1 receptor antagonist, betaxolol, and the selective beta 2 receptor antagonist, ICI 118,551. Further, a correlation analysis across each of the above agonists, as well as 8-OH-DPAT, buspirone, and (+)-flesinoxan, revealed a significant correlation for their relative potency in augmenting punished responding and their affinity for 5-HT1A receptors in vitro (r = +0.95, p < 0.001). It is concluded that S 14671 is an exceptionally potent and efficacious ligand in the pigeon conflict test and that its anxiolytic action reflects the activation of 5-HT1A receptors.

UI MeSH Term Description Entries
D008297 Male Males
D010856 Columbidae Family in the order COLUMBIFORMES, comprised of pigeons or doves. They are BIRDS with short legs, stout bodies, small heads, and slender bills. Some sources call the smaller species doves and the larger pigeons, but the names are interchangeable. Columba livia,Doves,Pigeons,Domestic Pigeons,Feral Pigeons,Rock Doves,Rock Pigeons,Domestic Pigeon,Dove,Dove, Rock,Doves, Rock,Feral Pigeon,Pigeon,Pigeon, Domestic,Pigeon, Feral,Pigeon, Rock,Pigeons, Domestic,Pigeons, Feral,Pigeons, Rock,Rock Dove,Rock Pigeon
D010879 Piperazines Compounds that are derived from PIPERAZINE.
D011678 Punishment The application of an unpleasant stimulus or penalty for the purpose of eliminating or correcting undesirable behavior. Punishments
D011985 Receptors, Serotonin Cell-surface proteins that bind SEROTONIN and trigger intracellular changes which influence the behavior of cells. Several types of serotonin receptors have been recognized which differ in their pharmacology, molecular biology, and mode of action. 5-HT Receptor,5-HT Receptors,5-Hydroxytryptamine Receptor,5-Hydroxytryptamine Receptors,Receptors, Tryptamine,Serotonin Receptor,Serotonin Receptors,Tryptamine Receptor,Tryptamine Receptors,Receptors, 5-HT,Receptors, 5-Hydroxytryptamine,5 HT Receptor,5 HT Receptors,5 Hydroxytryptamine Receptor,5 Hydroxytryptamine Receptors,Receptor, 5-HT,Receptor, 5-Hydroxytryptamine,Receptor, Serotonin,Receptor, Tryptamine,Receptors, 5 HT,Receptors, 5 Hydroxytryptamine
D003220 Conflict, Psychological The internal individual struggle resulting from incompatible or opposing needs, drives, or external and internal demands. In group interactions, competitive or opposing action of incompatibles: antagonistic state or action (as of divergent ideas, interests, or persons). (from Merriam-Webster's Collegiate Dictionary, 10th ed) Conflict, Psychology,Psychological Conflict,Psychological Conflicts
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D004347 Drug Interactions The action of a drug that may affect the activity, metabolism, or toxicity of another drug. Drug Interaction,Interaction, Drug,Interactions, Drug
D005260 Female Females
D000526 Alprenolol One of the ADRENERGIC BETA-ANTAGONISTS used as an antihypertensive, anti-anginal, and anti-arrhythmic agent. 1-(o-Allylphenoxy)-3-(isopropylamino)-2-propanol,Alfeprol,Alpheprol,Alprenolol Hydrochloride,Aptin,Aptin-Duriles,Aptina,Aptine,H-56-28,Aptin Duriles,AptinDuriles,H 56 28,H5628

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