EFFECTS OF 5-HT1A RECEPTOR LIGANDS IN A MODIFIED GELLER-SEIFTER CONFLICT MODEL IN THE RAT

In a modified Geller-Seifter conflict procedure, rats were trained to lever-press for food under a multiple variable interval-fixed ratio (V I30: food; FRIO: food + shock) schedule of reinforcement. The ability to antagonize response suppression in the punished period is considere d a good predictor for anxiolytic activity. Chlordiazepoxide and alpra zolam increased punished responding. The 5-HT1A receptor agonists fles inoxan xin-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 m g/kg) significantly increased punished re spending, supporting a role of the 5-HT1A receptor in anxiety. 8-OH-DPAT and flesinoxan also reduc ed unpunished responding. The anxiolytic effects of 8-OH-DPAT and fles inoxan could only be antagonized with a high dose (1.0 and 3.0 mg/kg r espectively) of the 5-HT1A receptor antagonist WAY-100635 ethoxyphenyl )-1-piperazinyl]ethyl]-N-(2-pyridinyl) cyclohexanecarboxamide trihydro chloride). All doses of WAY-100635 antagonized the 5-HT1A-induced effe cts on unpunished responding. The dissimilarity in dose-response curve of WAY-100635 on punished and unpunished behaviour poses questions ab out the mediation of these effects. (C) 1997 Elsevier Science B.V.