title: The cannabinoid receptor CB₁ inverse agonist AM251 potentiates the anxiogenic activity of urocortin I in the basolateral amygdala.
abstract: The basolateral amygdala is reported to play an important role in the neural bases of emotional processing. Previous studies have shown that injections of urocortin I (UcnI) into the basolateral amygdala (BLA) elicit anxiety-like behaviors in animal models. The present study examined the anxiogenic effects of UcnI administered directly into the BLA of male Sprague-Dawley rats. UcnI was administered at doses of 0.1-10.0 pmol and rats were then placed in an elevated plus maze for 10 min. UcnI reliably decreased the percent time spent in the open arms of the elevated plus maze (EPM) as well as open arm entries. This effect was observed across all doses tested, indicating the induction of anxiety-like behavior. In separate groups of rats, the CB(1) inverse agonist AM251 was administered systemically (0.03-3.0 mg/kg IP) or directly into the BLA (0.25-25.0 pmol) and EPM performance assessed. Both routes of AM251 administration produced a reduction in open arm entries and in time spent in the open arms. Moreover, when rats were pretreated with AM251 either systemically or directly into the BLA, the anxiogenic effect of UcnI was potentiated. That is, co-administration of AM251 and UcnI produced a greater suppression of percent time spent in the open arms and open arm entries as compared to UcnI alone. Based on these findings, we propose that urocortin and endocannabinoid signaling are part of an integrated neural axis modulating anxiety states within the basolateral amygdala. This article is part of a Special Issue entitled 'Anxiety and Depression'.
authors: Department of Psychology, Reed College, 3203 SE Woodstock Blvd, Portland, OR 97202, USA.
authors: Lindsey M
authors: LM
authors: Dono
authors: Paul J
authors: PJ
authors: Currie
mesh_terms: D000679:Amygdala / Q000378:metabolism*; D000818:Animals; D014151:Anti-Anxiety Agents / Q000627:therapeutic use*; D001007:Anxiety / Q000188:drug therapy* / Q000473:pathology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005106:Exploratory Behavior / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D010880:Piperidines / Q000627:therapeutic use*; D011720:Pyrazoles / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D054832:Urocortins / Q000378:metabolism*
chemical_list: D014151:Anti-Anxiety Agents; D010880:Piperidines; D011720:Pyrazoles; D054832:Urocortins; C103505:AM 251