PMID- 10686300
OWN - NLM
STAT- MEDLINE
DCOM- 20000420
LR  - 20191210
IS  - 0014-2999 (Print)
IS  - 0014-2999 (Linking)
VI  - 389
IP  - 1
DP  - 2000 Feb 11
TI  - Endogenous corticotropin-releasing hormone inhibits conditioned-fear-induced 
      vagal activation in the rat.
PG  - 89-98
AB  - The role of the endogenous corticotropin-releasing hormone (CRH) system in the 
      regulation of heart rate, PQ interval (a measure of vagal activity), gross 
      activity and release of adrenocorticotropic hormone (ACTH), noradrenaline and 
      adrenaline into the blood during conditioned fear was studied in freely moving 
      rats. Intracerebroventricular (i.c.v.) infusion of alpha-helical CRH-(9-41) (10 
      microgram/3 microliter), a non-selective CRH receptor antagonist, under resting 
      conditions had no significant effect on gross activity, heart rate and PQ 
      interval, indicating that alpha-helical CRH at this dose was devoid of agonist 
      effects. Conditioned fear was induced by 10 min forced exposure to a cage in 
      which the rat had experienced footshocks (5x0.5 mAx3 s) 1 day before. 
      Conditioned-fear rats showed freezing behaviour, associated with an increase in 
      heart rate, PQ interval, noradrenaline and adrenaline, indicating that the 
      conditioned-fear-induced cardiac effects were the result of coactivation of the 
      sympathetic and parasympathetic nervous system. The i.c.v. pre-treatment of rats 
      with alpha-helical CRH significantly reduced the conditioned-fear-induced 
      tachycardiac and ACTH response, and enhanced the increase in PQ interval, without 
      affecting the noradrenaline and adrenaline response. These results suggest that 
      endogenous CRH reduces the vagal response to conditioned-fear stress in rats. To 
      test this, rats were pre-treated with atropine methyl nitrate (0.3 mg/kg, 
      subcutaneously; s.c.), a peripherally acting cholinergic receptor antagonist. 
      This resulted in a complete blockade of the alpha-helical CRH-induced decrease in 
      heart rate response and increase in PQ interval. From these findings, it is 
      concluded that endogenous CRH in the brain inhibits vagal outflow induced by 
      emotional stress.
FAU - Nijsen, M J
AU  - Nijsen MJ
AD  - Department of Medical Pharmacology, Rudolf Magnus Institute for Neurosciences, 
      Utrecht University, Utrecht, Netherlands. nijsen@med.uu.nl
FAU - Croiset, G
AU  - Croiset G
FAU - Diamant, M
AU  - Diamant M
FAU - Stam, R
AU  - Stam R
FAU - Kamphuis, P J
AU  - Kamphuis PJ
FAU - Bruijnzeel, A
AU  - Bruijnzeel A
FAU - de Wied, D
AU  - de Wied D
FAU - Wiegant, V M
AU  - Wiegant VM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - Eur J Pharmacol
JT  - European journal of pharmacology
JID - 1254354
RN  - 0 (alpha helical corticotropin-releasing hormone)
RN  - 9002-60-2 (Adrenocorticotropic Hormone)
RN  - 9015-71-8 (Corticotropin-Releasing Hormone)
RN  - X4W3ENH1CV (Norepinephrine)
RN  - YKH834O4BH (Epinephrine)
SB  - IM
MH  - Adrenocorticotropic Hormone/blood
MH  - Animals
MH  - Behavior, Animal/drug effects
MH  - Conditioning, Psychological/*drug effects
MH  - Corticotropin-Releasing Hormone/pharmacology/*physiology
MH  - Electrocardiography
MH  - Epinephrine/blood
MH  - Fear/*drug effects
MH  - Heart Rate/drug effects
MH  - Injections, Intraventricular
MH  - Male
MH  - Norepinephrine/blood
MH  - Parasympathetic Nervous System/drug effects
MH  - Rats
MH  - Rats, Wistar
MH  - Sympathetic Nervous System/drug effects
MH  - Vagus Nerve/drug effects/*physiology
EDAT- 2000/02/25 09:00
MHDA- 2000/04/25 09:00
CRDT- 2000/02/25 09:00
PHST- 2000/02/25 09:00 [pubmed]
PHST- 2000/04/25 09:00 [medline]
PHST- 2000/02/25 09:00 [entrez]
AID - S0014-2999(99)00870-5 [pii]
AID - 10.1016/s0014-2999(99)00870-5 [doi]
PST - ppublish
SO  - Eur J Pharmacol. 2000 Feb 11;389(1):89-98. doi: 10.1016/s0014-2999(99)00870-5.