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 (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-HT1A 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-HT1A 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-HT1A 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-HT1A-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.
King
C M
CM
Department of Psychopharmacology, Faculty of Pharmacy, and Rudolf Magnus Institute for Neurosciences, Utrecht University, Netherlands.
Gommans
J
J
Joordens
R J
RJ
Hijzen
T H
TH
Maes
R A
RA
Olivier
B
B
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000525:Alprazolam / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects* / Q000502:physiology*; D002707:Chlordiazepoxide / Q000494:pharmacology; D003220:Conflict, Psychological; D008024:Ligands; D008297:Male; D010879:Piperazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D019257:Quinpirole / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000502:physiology*; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology
D008024:Ligands; D010879:Piperazines; D011725:Pyridines; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D019257:Quinpirole; C056895:flesinoxan; D002707:Chlordiazepoxide; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000525:Alprazolam