Effect of 5-HT5A antagonists in animal models of schizophrenia, anxiety and depression.
The few available data on the pharmacological effect of 5-HT5A receptors suggest that antagonists may have anxiolytic, antidepressant and antipsychotic activity. The aim of our study was to verify these suggestions in relevant animal models. Two 5-HT5A antagonist ligands, SB-699551-A (N-[2-(dimethylamino)ethyl]-N-[[4'-[[(2-phenylethyl)amino]methyl][1,1'-biphenyl]-4-yl]methyl]cyclopentanepropanamide dihydrochloride) (3-60 mg/kg, intraperitoneally) and A-843277 (N-(2,6-dimethoxybenzyl)-N'[4-(4-fluorophenyl)thiazol-2-yl]guanidine) (3-30 mg/kg, intraperitoneally), were examined in the open-field test, in a foot-shock-induced ultrasonic vocalization test, in the forced swim test (FST) and in the amphetamine-induced and phencyclidine-induced hyperlocomotion tests to examine their effect on general behavioural patterns, and their anxiolytic-like, antidepressant-like and antipsychotic-like properties, respectively. In the open-field test, SB-699551-A induced sedation and A-843277 induced writhing. In the ultrasonic vocalization test, SB-699551-A reduced vocalizations, whereas A-843277 was ineffective. In the FST, SB-699551-A was ineffective and A-843277 reduced immobility, but only at the highest dose. In the amphetamine-induced and phencyclidine-induced hyperlocomotion test, both compounds were ineffective. SB-699551-A showed an anxiolytic-like property in the ultrasonic vocalization test; however, this compound has a sedative effect. A-843277 showed an antidepressant-like property in the FST, but its immobility-reducing effect may also be a consequence of abdominal irritation. Consequently, further investigations are required to define the therapeutic potential of 5-HT5A receptor ligands in anxiety, depression and schizophrenia models.
Department of Behavioural Pharmacology, Budapest, Hungary. fe.kassai@richter.hu
Ferenc
F
Kassai
Chantal
C
Schlumberger
Rita
R
Kedves
Malgorzata
M
Pietraszek
Claudia
C
Jatzke
Balázs
B
Lendvai
István
I
Gyertyán
Wojciech
W
Danysz
D000818:Animals; D014151:Anti-Anxiety Agents / Q000008:administration & dosage / Q000494:pharmacology; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000494:pharmacology; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000494:pharmacology; D001007:Anxiety / Q000188:drug therapy / Q000503:physiopathology; D001713:Biphenyl Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D003863:Depression / Q000188:drug therapy / Q000503:physiopathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006146:Guanidines / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000378:metabolism; D012559:Schizophrenia / Q000188:drug therapy / Q000503:physiopathology; D012702:Serotonin Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D013550:Swimming; D013844:Thiazoles / Q000008:administration & dosage / Q000494:pharmacology*; D014828:Vocalization, Animal / Q000187:drug effects
D014151:Anti-Anxiety Agents; D000928:Antidepressive Agents; D014150:Antipsychotic Agents; D001713:Biphenyl Compounds; D006146:Guanidines; C576531:N-(2,6-dimethoxybenzyl)-N'-(4-(4-fluorophenyl)thiazol-2-yl)guanidine; D011985:Receptors, Serotonin; C515421:SB-699551-A; D012702:Serotonin Antagonists; D013844:Thiazoles; C078730:serotonin 5 receptor