Antagonism of corticotropin-releasing factor receptors in the locus coeruleus attenuates shock-induced freezing in rats.
Intracerebroventricularly administered alpha-helical CRF9-41, a corticotropin-releasing factor (CRF) receptor antagonist, is known to reduce a variety of stress-induced behavioral responses. This study examined in rats whether antagonism of CRF receptors in the region of locus coeruleus (LC) plays a role in reducing freezing induced by electric foot shock. Freezing is a well-characterized defensive response to stress and has been demonstrated to index an animal's degree of fear. A CRF-receptor antagonist, alpha-helical CRF9-41, bilaterally infused into the LC significantly reduced the duration of freezing at a dose as low as 0.20 micrograms. Additional experiments confirmed that 0.20 micrograms of alpha-helical CRF9-41 significantly reduced the duration of freezing only when cannulae were within the LC or in regions bordering the nucleus. Antagonist-treated rats with cannulae that did not impinge on the LC exhibited freezing at levels not different from vehicle-treated animals. These results strongly implicate CRF receptors located in the LC region in influencing the display of stress-induced behavior.
Swiergiel
A H
AH
Department of Psychiatry, University of Wisconsin Medical School, Madison 53792.
Takahashi
L K
LK
Rubin
W W
WW
Kalin
N H
NH
D000818:Animals; D003346:Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004597:Electroshock; D007276:Injections, Intraventricular; D008125:Locus Coeruleus / Q000033:anatomy & histology / Q000378:metabolism*; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D018019:Receptors, Corticotropin-Releasing Hormone; D017981:Receptors, Neurotransmitter / Q000037:antagonists & inhibitors*; D013315:Stress, Psychological / Q000523:psychology
D018019:Receptors, Corticotropin-Releasing Hormone; D017981:Receptors, Neurotransmitter; C069206:alpha helical corticotropin-releasing hormone; D003346:Corticotropin-Releasing Hormone