Importance of CRF receptor-mediated mechanisms of the bed nucleus of the stria terminalis in the processing of anxiety and pain.
Corticotropin-releasing factor (CRF)-mediated mechanisms in the bed nucleus of the stria terminalis (BNST) have a pivotal role in stress-induced anxiety and hyperalgesia. Although CRF is known to activate two receptor subtypes, CRF1 and CRF2, attempts to delineate the specific role of each subtype in modulating anxiety and nociception have been inconsistent. Here we test the hypothesis that CRF1 and CRF2 receptor activation in the anteriolateral BNST (BNSTAL) facilitates divergent mechanisms modulating comorbid anxiety and hyperalgesia. Microinfusions of the specific antagonists CP376395 and Astressin2B into the BNSTAL were used to investigate CRF1 and CRF2 receptor functions, respectively. We found that CRF1 and CRF2 receptors in the BNSTAL had opposing effects on exploratory behavior in the elevated plus-maze, somatic mechanical threshold, and the autonomic and endocrine response to stress. However, CRF1 or CRF2 receptor antagonism in the BNSTAL revealed complementary roles in facilitating the acoustic startle and visceromotor reflexes. Our results suggest that the net effect of CRF1 and CRF2 receptor activation in the BNSTAL is pathway-dependent and provides important insight into the CRF receptor-associated circuitry that likely underpins stress-induced pathologies.
Oklahoma Center for Neuroscience, University of Oklahoma Health Science Center, Oklahoma City, OK, USA.
Lee
L
Tran
Department of Neuroscience, Georgetown University, Washington, DC, USA.
Jay
J
Schulkin
1] Oklahoma Center for Neuroscience, University of Oklahoma Health Science Center, Oklahoma City, OK, USA [2] Department of Physiology, University of Oklahoma Health Science Center, Oklahoma City, OK, USA [3] VA Medical Center, Oklahoma City, OK, USA.
Beverley
B
Greenwood-Van Meerveld
D000631:Aminopyridines / Q000494:pharmacology; D000818:Animals; D001007:Anxiety / Q000188:drug therapy / Q000453:epidemiology / Q000503:physiopathology*; D002491:Central Nervous System Agents / Q000494:pharmacology; D015897:Comorbidity; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology; D006930:Hyperalgesia / Q000188:drug therapy / Q000453:epidemiology / Q000503:physiopathology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D010146:Pain / Q000188:drug therapy / Q000453:epidemiology / Q000503:physiopathology*; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology; D010446:Peptide Fragments / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D010812:Physical Stimulation; D011916:Rats, Inbred F344; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors / Q000378:metabolism*; D055139:Sensory Gating / Q000187:drug effects / Q000502:physiology; D012686:Septal Nuclei / Q000187:drug effects / Q000503:physiopathology*; D013315:Stress, Psychological / Q000188:drug therapy / Q000503:physiopathology; D000099052:CRF Receptor, Type 1
C529296:(3,6-dimethyl-2-(2,4,6-trimethylphenoxy)pyridin-4-yl)(1-ethylpropyl)amine; D000631:Aminopyridines; C101531:CRF receptor type 2; D002491:Central Nervous System Agents; D010446:Peptide Fragments; D010456:Peptides, Cyclic; D018019:Receptors, Corticotropin-Releasing Hormone; C528574:astressin-2B; D000099052:CRF Receptor, Type 1