In a modified Geller-Seifter conflict procedure, rats were trained to lever-press for food under a multiple variable interval-fixed ratio (VI30: food; FR10: food+shock) schedule of reinforcement. The ability to antagonize response suppression in the punished period is considered a good predictor for anxiolytic activity. Chlordiazepoxide and alprazolam increased punished responding. The 5-HT 1A receptor agonists flesinoxan ( R (+)- N -(2(4-(2,3-dihydro-2-2-hydroxymethyl-1,4-benzodioxin-5-yl)-1-piperazinyl)ethyl)-4-fluorobenzoamide; 0.1–10.0 mg/kg) and 8-OH-DPAT (8-hydroxy-2-(di- n -propyl-amino)tetralin; 0.03–0.5 mg/kg) significantly increased punished responding, supporting a role of the 5-HT 1A receptor in anxiety. 8-OH-DPAT and flesinoxan also reduced unpunished responding. The anxiolytic effects of 8-OH-DPAT and flesinoxan could only be antagonized with a high dose (1.0 and 3.0 mg/kg respectively) of the 5-HT 1A receptor antagonist WAY-100635 ( N -(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)- N -(2-pyridinyl) cyclohexanecarboxamide trihydrochloride). All doses of WAY-100635 antagonized the 5-HT 1A -induced effects on unpunished responding. The dissimilarity in dose-response curve of WAY-100635 on punished and unpunished behaviour poses questions about the mediation of these effects. © 1997 Elsevier Science B.V.
European Journal of Pharmacology – Elsevier
Published: May 1, 1997
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