Selective CRF2 receptor agonists ameliorate the anxiety- and depression-like state developed during chronic nicotine treatment and consequent acute withdrawal in mice.
The aim of the present study was to investigate the effects of the selective agonists of the corticotropin-releasing factor (CRF) 2 receptor, urocortin 2 (UCN 2) and urocortin 3 (UCN 3), on the anxiety- and depression-like signs induced by acute nicotine withdrawal in mice. In order to do so, male CFLP mice were exposed for 7 days to repeated intraperitoneal (IP) injection with nicotine or saline solution and 1day of acute withdrawal and then a single intracerebroventricular (ICV) injection with UCN 2, UCN 3 or saline solution. After 30min the mice were observed in an elevated plus-maze test or a forced swim test, for anxiety- and depression-like behavior. After 5min of testing, the plasma corticosterone concentration reflecting the activity of the hypothalamic-pituitary-adrenal (HPA) axis was also determined by a chemo-fluorescent method. Half of the animals were treated ICV and evaluated on the 8th day, the other half on the 9th day. On the 8th day, nicotine-treated mice presented signs of anxiolysis and depression, but no significant elevation of the plasma corticosterone concentration. On the 9th day, nicotine-treated mice exhibited signs of anxiety and depression and a significant increase of the plasma corticosterone levels. Central administration of UCN 2 or UCN 3 ameliorated the anxiety- and depression-like state including the hyperactivity of the HPA axis, developed during acute withdrawal following chronic nicotine treatment. The present study suggests that selective CRF2 receptor agonists could be used as a therapy in nicotine addiction.
Department of Pathophysiology, Faculty of Medicine, University of Szeged, Hungary. Electronic address: bagosi.zsolt@med.u-szeged.hu.
Zsolt
Z
Bagosi
Department of Pathophysiology, Faculty of Medicine, University of Szeged, Hungary.
Miklós
M
Palotai
Department of Pathophysiology, Faculty of Medicine, University of Szeged, Hungary.
Balázs
B
Simon
Department of Pathophysiology, Faculty of Medicine, University of Szeged, Hungary.
Péter
P
Bokor
Department of Pathophysiology, Faculty of Medicine, University of Szeged, Hungary.
András
A
Buzás
Department of Pathophysiology, Faculty of Medicine, University of Szeged, Hungary.
Beáta
B
Balangó
Department of Pathophysiology, Faculty of Medicine, University of Szeged, Hungary.
Dávid
D
Pintér
Department of Pathophysiology, Faculty of Medicine, University of Szeged, Hungary.
Miklós
M
Jászberényi
Department of Pathophysiology, Faculty of Medicine, University of Szeged, Hungary.
Krisztina
K
Csabafi
Department of Pathophysiology, Faculty of Medicine, University of Szeged, Hungary.
Gyula
G
Szabó
D000818:Animals; D001007:Anxiety / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D003345:Corticosterone / Q000097:blood; D003863:Depression / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000378:metabolism; D057967:Infusions, Intraventricular; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009538:Nicotine / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000378:metabolism; D011619:Psychotropic Drugs / Q000008:administration & dosage*; D018019:Receptors, Corticotropin-Releasing Hormone / Q000819:agonists* / Q000378:metabolism; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy* / Q000378:metabolism / Q000523:psychology; D014029:Tobacco Use Disorder / Q000188:drug therapy* / Q000378:metabolism / Q000523:psychology; D054832:Urocortins / Q000008:administration & dosage
C101531:CRF receptor type 2; D018722:Nicotinic Agonists; D011619:Psychotropic Drugs; D018019:Receptors, Corticotropin-Releasing Hormone; D054832:Urocortins; D009538:Nicotine; D003345:Corticosterone
Anxiety; Corticosterone; Depression; Mice; Nicotine; Urocortin