Serotonin 2C receptors within the basolateral amygdala induce acute fear-like responses in an open-field environment.
Several studies indicate a role for the serotonin 2 subfamily (5-HT(2A), 5-HT(2B), 5-HT(2C)) in mediation of fear and anxiety responses. The current study began to examine the effects of stimulating 5-HT(2C) receptors within the basolateral (BLA) or central nucleus of the amygdala (CeA) on acute fear-like responses in rats. Bilateral intra-BLA infusions of mCPP (3-3000 pmol), a mixed 5-HT(2) agonist, produced ultrasonic vocalization and reduced exploratory behavior while increasing the latency to investigate a novel object. These responses were attenuated by SB-242084, a 5-HT(2C)-specific antagonist. Furthermore, a selective 5-HT(2C) agonist, IL-639, produced a similar repertoire of behavioral effects with the exception of effects on time spent in the center of an open-field arena. Finally, infusions of mCPP into the CeA produced no anxiogenic behaviors suggesting that 5-HT(2C) receptors primarily within the BLA are responsible for many of the acute fear-like responses reported here. To characterize further the neural circuits associated with 5-HT(2C)-mediated fear responses, we assessed c-fos mRNA expression after intra-BLA infusions of mCPP, IL-639 or their vehicles. Whereas the overall regional pattern of c-fos mRNA induction for the two compounds was distinct, c-fos activation was confined primarily to limbic nuclei with the medial prefrontal cortex as a common regional target of each drug. These results suggest that activation of 5-HT(2C) receptors within the BLA influences the activity of limbic circuits involved in the expression of acute innate fear responses.
Campbell
Brian M
BM
Department of Biology II/Neurobiology, Pfizer Inc., MS 7251-209-507, 301 Henrietta St., Kalamazoo, MI 49007, USA. brian.campbell@pharmacia.com
Merchant
Kalpana M
KM
D000631:Aminopyridines / Q000494:pharmacology; D000679:Amygdala / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001007:Anxiety / Q000139:chemically induced / Q000378:metabolism; D001522:Behavior, Animal / Q000187:drug effects; D018891:Dentate Gyrus / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005106:Exploratory Behavior / Q000187:drug effects; D005239:Fear / Q000502:physiology*; D017403:In Situ Hybridization; D007211:Indoles / Q000494:pharmacology; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D017397:Prefrontal Cortex / Q000187:drug effects; D011422:Propionates / Q000494:pharmacology; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D044405:Receptor, Serotonin, 5-HT2C / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D013788:Thalamus / Q000187:drug effects / Q000378:metabolism; D014465:Ultrasonics; D014828:Vocalization, Animal / Q000187:drug effects
C107820:6-chloro-5-methyl-1-((2-(2-methylpyrid-3-yloxy)pyrid-5-yl)carbamoyl)indoline; D000631:Aminopyridines; D007211:Indoles; D011422:Propionates; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D044405:Receptor, Serotonin, 5-HT2C; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; C029658:propionic acid