Effects of a selective 5-HT1B receptor agonist and antagonists in animal models of anxiety and depression.
The purpose of the present study was to investigate the effects of the selective 5-HT1B receptor agonist CP 94253, the selective 5-HT1B receptor antagonist SB 216641, and the 5-HT1B/1D receptor antagonist GR 127935 in behavioral tests commonly used to predict anxiolytic- and antidepressant-like activity. Diazepam and imipramine were used as reference drugs. In the Vogel conflict drinking test, CP 94253 (1.25-5 mg/kg), SB 216641 (2.5-5 mg/kg) and GR 127935 (5-10 mg/kg) showed anxiolytic-like effects comparable to that of diazepam (2.5-5 mg/kg). In the elevated plus-maze test, antianxiety-like activity of all the compounds tested was also observed: the effects of CP 94253 (2.5 mg/kg) and SB 216641 (5 mg/kg) were similar to that of diazepam (5 mg/kg), while GR 127935 (up to 40 mg/kg) was less active. In the four-plate test, the compounds tested (5-10 mg/kg) produced anxiolytic-like effects which were weaker than that of diazepam (2.5-5 mg/kg). In the forced swimming test, CP 94253 (5-10 mg/kg), like imipramine (30 mg/kg), showed anti-immobility action, whereas SB 216641 (2.5-10 mg/kg) and GR 127935 (20-40 mg/kg) did not affect the immobility time in mice. The results indicate that the selective agonist (CP 94253) and antagonists (SB 216641 and GR 127935) of 5-HT1B receptors produce effects that are characteristic of anxiolytics, in the preclinical models used; however, CP 94253 also behaves like an antidepressant drug.
Tatarczyńska
E
E
Institute of Pharmacology, Polish Academy of Sciences, 12 Smêtna Street, 31-343 Kraków, Poland. wojcik@if-pan.krakow.pl
Kłodzińska
A
A
Stachowicz
K
K
Chojnacka-Wójcik
E
E
D000818:Animals; D014151:Anti-Anxiety Agents / Q000627:therapeutic use; D000929:Antidepressive Agents, Tricyclic / Q000627:therapeutic use; D001007:Anxiety / Q000188:drug therapy* / Q000523:psychology; D001522:Behavior, Animal / Q000187:drug effects; D001549:Benzamides / Q000627:therapeutic use; D003220:Conflict, Psychological; D003866:Depressive Disorder / Q000188:drug therapy* / Q000523:psychology; D003975:Diazepam / Q000627:therapeutic use; D004597:Electroshock; D005106:Exploratory Behavior / Q000187:drug effects; D007099:Imipramine / Q000627:therapeutic use; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D010069:Oxadiazoles / Q000627:therapeutic use; D010879:Piperazines / Q000627:therapeutic use; D011725:Pyridines / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects; D044302:Receptor, Serotonin, 5-HT1B / Q000187:drug effects*; D012702:Serotonin Antagonists / Q000627:therapeutic use*; D017366:Serotonin Receptor Agonists / Q000627:therapeutic use*; D013550:Swimming / Q000523:psychology
D014151:Anti-Anxiety Agents; D000929:Antidepressive Agents, Tricyclic; D001549:Benzamides; C097067:CP 94253; C108531:N-(3-(2-dimethylamino)ethoxy-4-methoxyphenyl)-2'-methyl-4'-(5-methyl-1,2,4-oxadiazol-3-yl)-(1,1'-biphenyl)-4-carboxamide; D010069:Oxadiazoles; D010879:Piperazines; D011725:Pyridines; D044302:Receptor, Serotonin, 5-HT1B; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; C090701:GR 127935; D007099:Imipramine; D003975:Diazepam