Local tetrodotoxin blocks chronic stress effects on corticotropin-releasing factor and vasopressin messenger ribonucleic acids in hypophysiotropic neurons.
To test the hypothesis that synaptic inputs to the paraventricular nucleus mediate stress-induced increases in corticotropin-releasing peptide expression in the paraventricular nucleus of the hypothalamus (PVH), relative levels of the mRNAs encoding corticotropin-releasing factor (CRF) and arginine vasopressin (AVP) were followed, in situ, in animals subjected to chronic footshock stress and concurrent local administration of tetrodotoxin or vehicle. Consistent with previous findings, a 7-day exposure to chronic footshock resulted in a 2.1-fold increase in CRF mRNA levels in the parvocellular division of the PVH. The footshock paradigm also resulted in at least a 41% increase in AVP transcripts in this same region; this effect was localized predominantly to CRF-immunoreactive neurons. The stressor did not significantly alter AVP mRNA levels in the magnocellular division of the PVH. Tetrodotoxin, administered to the PVH via osmotic minipump, blocked the stress-induced rise in CRF and AVP mRNAs, but had no significant effect on basal levels of these transcripts. The results support the view that maintenance of the enhanced central drive on pituitary-adrenal activity seen in response to chronic stress is mediated via neural inputs to the PVH.
Sawchenko
P E
PE
Salk Institute for Biological Studies, La Jolla, California 92037.
Arias
C A
CA
Mortrud
M T
MT
D000818:Animals; D001127:Arginine Vasopressin / Q000235:genetics*; D003346:Corticotropin-Releasing Hormone / Q000235:genetics*; D004597:Electroshock; D008297:Male; D010286:Paraventricular Hypothalamic Nucleus / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013312:Stress, Physiological / Q000378:metabolism*; D013779:Tetrodotoxin / Q000494:pharmacology*
D012333:RNA, Messenger; D001127:Arginine Vasopressin; D013779:Tetrodotoxin; D003346:Corticotropin-Releasing Hormone