v

ANXIOLYTIC-LIKE EFFECT OF BETA RECEPTOR AGONIST AMIBEGRON (SR 58611A) WHICH MAY BE RELATED TO INTERACTION OF SEROTONIN RECEPTOR SUBTYPES 1 1 2 2 2 2 2 Pelin Tanyeri , Mehmet Emin Büyükokuroğlu , Oguz Mutlu , Güner Ulak , Füruzan Yıldız Akar , İpek Komşuoğlu Çelikyurt , Bekir Faruk Erden 1 Sakarya University, Faculty of Medicine, Department of Pharmacology, 54100-Sakarya/Turkey, 2 Kocaeli University, Faculty of Medicine, Department of Pharmacology, 41380-Kocaeli/Turkey

OBJECTIVES THE AIM OF THE STUDY MATERIAL-METHODS

Anxiety disorders are the most common and prevalent behavioral disorders with high comor- This study is aimed to investigate the effects of the first selective beta3 adrenergic agent ami- We used the serotonin 5HT1A receptor antagonist WAY-100635, serotonin 5HT2A-2C re- bidity rates. The decrease of the serotonergic activity and dysregulation of catecholaminer- begron on anxiety and also the involvement of different serotonin receptor subtypes in this ceptor antagonist ketanserin and serotonin 5HT3 receptor antagonist ondansetron in the ele- gic system may play a role in the pathogenesis of anxiety. effect. vated plus maze test.

RESULTS CONCLUSION DISCLOSURE PANELS

Amibegron (5 and 10 mg/kg) dose dependently prolonged the time spent in open arms and the number of entries to the open arms in mice EPM test. WAY, ketanserin and ondanset- In conclusion, amibegron exerted significant anxiolytic-like ef- Nothing to disclose ron had no effect on the time spent in open arms and the number of entries to the open arms in mice and also they all significantly reversed amibegron (10 mg/kg)-induced increase in fects in the mice EPM test which was as effective as diazepam. the time spent in open arms while only WAY and ketanserin reversed amibegron-induced increase in number of entries to the open arms. The influence of the treatments on locomotor This effect of amibegron may be mediated by an interaction activity was evaluated by one-way ANOVA. None of the administered treatments modified the total distance moved or the speed of the animals with serotonin 5-HT1A, 5-HT2A-2C and 5-HT3 receptors.

a a a a 3500 saline

bnz 2 mg/kg 3000

80 80 80 70 amb 5 mg/kg 70 70 70 60 2500 amb 10 mg/kg 60 60 60 50 saline saline saline saline 2000 WAY 0,1 mg/kg 50 50 50 saline+DMSO saline+DMSO saline+DMSO 40 saline +DMSO WAY 0,1 + amb 10 mg/kg 40 bnz 2 mg/kg 40 WAY 0,1 mg/kg 40 ket 5 mg/kg ond 1 mg/kg 1500 amb 5 mg/kg amb 10 mg/kg amb 10 mg/kg 30 amb 10 mg/kg 30 30 30 ket 5 mg/kg WAY 0,1+amb 10 mg/kg ket 5 +amb 10 mg/kg distance moved (cm) 1000 amb 10 mg/kg 20 ond 1 + amb 10 mg/kg 20 20 20 ket 5 + amb 10 mg/kg 500 10 10 10 10 ond 1 mg/kg time spent in open arms (s) arms open in spent time (s) arms open in spent time time spent in open arms (s) arms open in spent time (s) arms open in spent time 0 0 0 0 0 ond 1 + amb 10 mg/kg

Effects of diazepam (bnz) (2 mg/kg) and amibegron (amb) (5 and 10 mg/kg) on the % time spent in open Effects of amibegron (amb) (10 mg/kg), WAY-100635 (WAY) (0,1 mg/kg) and combination of ami- Effects of amibegron (amb) (10 mg/kg), ketanserin (ket) (5 mg/kg) and combination of amibegron Effects of amibegron (amb) (10 mg/kg), ondansetron (ond) (1 mg/kg) and combination of amibegron Effects of diazepam (2 mg/kg), amibegron (5 and 10 mg/kg), WAY-100635 (0,1 mg/kg), WAY- arms in mice EPM test. Each column represents the mean ± S.E.M.of 9-10 animals. *p<0.01; ** p<0.001 begron and WAY-100635 on the % time spent in open arms in mice EPM test. Each column repre- and ketanserin on the % time spent in open arms in mice EPM test. Each column represents the me- and ondansetron on the % time spent in open arms in mice EPM test. Each column represents the me- 100635 (0,1 mg/kg) + amibegron (10 mg/kg), ketanserin (5 mg/kg), ketanserin (5mg/kg) + ami- compared to vehicle control (Tukey test) sents the mean±S.E.M. of 9-10 animals. an±S.E.M. of 9-10 animals. an±S.E.M. of 9-10 animals. begron (10 mg/kg), ondansetron (1 mg/kg), ondansetron (1 mg/kg) + amibegron(10 mg/kg) on total * p<0.001 compared to vehicle control (Tukey test); # p<0.001 compared to amibegron 10 mg/kg *p<0.001 compared to vehicle control (Tukey test); # p<0.001 compared to amibegron 10 mg/kg *p<0.001 compared to vehicle control (Tukey test); # p<0.01 compared to amibegron 10 mg/kg distance moved in the open field test. Each column represents themean±S.E.M.of 8 animals. (Tukey test) (Tukey test) (Tukey test) p>0.05 compared to vehicle control (Tukey test)

saline b b b anxiety 12 bnz 2 mg/kg

80 80 80 80 10 amb 5 mg/kg 70 70 70 70

amb 10 mg/kg 8 60 60 60 60 saline WAY 0,1 mg/kg 50 saline saline saline saline+DMSO 50 50 50 6 saline+DMSO saline+DMSO saline+DMSO WAY 0,1 mg/kg + amb 10 40 bnz 2 mg/kg

arms (%) 40 WAY 0,1 mg/kg 40 ket 5 mg/kg 40 ond 1 mg/kg mg/kg arms (%) arms (%) arms (%)

amb 5 mg/kg (cm/s) speed 30 amb 10 mg/kg amb 10 mg/kg amb 10 mg/kg 4 ket 5 mg/kg amb 10 mg/kg 30 30 30 WAY 0,1+amb 10 mg/kg ket 5 + amb 10 mg/kg ond 1 +amb 10 mg/kg 20 ket 5 + amb 10 mg/kg 20 20 20

number of entrance in open 10 2

number of entrance in open 10 number of entrance in open 10 number of entrance in open 10 ond 1 mg/kg 0 0 0 0 0 ond 1 + amb 10 mg/kg

Effects of diazepam (2 mg/kg) and amibegron (5 and 10 mg/kg) on the % number of entries to the open Effects of amibegron (10 mg/kg), WAY-100635 (0,1 mg/kg) and combination of amibegron and Effects of amibegron (10 mg/kg), ketanserin (5 mg/kg) and combination of amibegron and ketan- Effects of amibegron (10 mg/kg), ondansetron (1 mg/kg) and combination of amibegron and on- Effects of diazepam (2 mg/kg), amibegron (5 and 10 mg/kg), WAY-100635 (0,1 mg/kg), WAY- arms in mice EPM test. Each column represents the mean ± S.E.M.of 9-10 animals. WAY-100635 on the % number of entries to the open arms in mice EPM test. Each column represents serin on the % number of entries to the open arms in mice EPM test. Each column represents the me- dansetron on the % number of entries to the open arms in mice EPM test. Each column represents the 100635 (0,1 mg/kg) + amibegron (10 mg/kg), ketanserin (5 mg/kg), ketanserin (5mg/kg) + ami- *p<0.05; ** p<0.001 compared to vehicle control (Tukey test) the mean±S.E.M. of 9-10 animals. an±S.E.M. of 9-10 animals. mean±S.E.M. of 9-10 animals. begron (10 mg/kg), ondansetron (1 mg/kg), ondansetron (1 mg/kg) + amibegron (10 mg/kg) on * p<0.001 compared to vehicle control (Tukey test); # p<0.001 compared to amibegron 10 mg/kg *p<0.001 compared to vehicle control (Tukey test); # p<0.001 compared to amibegron 10 mg/kg *p<0.001 compared to vehicle control (Tukey test); # p<0.01 compared to amibegron 10 mg/kg speed of the animals in the open field test. Each column represents the mean±S.E.M.of 8 animals. (Tukey test) (Tukey test) (Tukey test) p>0.05 compared to vehicle control (Tukey test)