PMID- 11222986
OWN - NLM
STAT- MEDLINE
DCOM- 20010621
LR  - 20190614
IS  - 0006-8993 (Print)
IS  - 0006-8993 (Linking)
VI  - 893
IP  - 1-2
DP  - 2001 Mar 2
TI  - Central corticotropin releasing factor (CRF) and adrenergic receptors mediate 
      hemodynamic responses to cocaine.
PG  - 1-10
AB  - Cocaine administration evokes cardiovascular responses that are variable in rats 
      such that the pressor response is attributable to either a large increase in 
      systemic vascular resistance and a decrease in cardiac output (vascular 
      responders) or a smaller increase in systemic vascular resistance and no change 
      or an increase in cardiac output (mixed responders). This study was designed to 
      determine the role of central corticotropin releasing factor (CRF) and adrenergic 
      receptors in mediating specific hemodynamic response patterns. Rats were 
      instrumented for ascending aortic blood flow determination (cardiac output) using 
      a pulsed Doppler system, arterial pressure measurement and for intravenous and 
      intracerebroventricular (icv) administration of drugs. After characterizing the 
      hemodynamic response pattern in individual rats to cocaine (5 mg/kg, i.v., 4-6 
      trials), selective receptor antagonists were administered icv 10 min before 
      cocaine (5 mg/kg, i.v.). Pretreatment with the CRF antagonist alpha-helical 
      CRF(9-41) (10 microg/5 microl, icv) prevented the decrease in cardiac output in 
      vascular responders without altering hemodynamic responses to cocaine in mixed 
      responders. Astressin (5 microg/5 microl, icv) exerted a similar effect in 
      vascular responders. The alpha(2) receptor antagonist, yohimbine (3 
      microg/microl, icv) also prevented the decrease in cardiac output in vascular 
      responders. Lower doses of alpha-helical CRF(9-41) (1 and 3 microg) were 
      ineffective whereas higher doses of either CRF antagonist were lethal within 24 
      h. In contrast, propranolol (3 or 30 microg, icv) pretreatment enhanced the 
      cocaine-induced decrease in cardiac output and increase in systemic vascular 
      resistance noted in vascular responders and resulted in a decrease in cardiac 
      output in mixed responders. We conclude that CRF and adrenoceptors in the CNS 
      play an important role in determining the hemodynamic response pattern to 
      cocaine. Furthermore, central beta-adrenoceptors may be responsible for the 
      reported effects of intravenous propranolol on cocaine-induced responses.
FAU - Dong, H W
AU  - Dong HW
AD  - Department of Pharmacological and Physiological Science, Saint Louis University 
      School of Medicine, 1402 S. Grand Blvd., St. Louis, MO 63104, USA. 
      hongwei@thalamus.wustl.edu
FAU - Gan, Q
AU  - Gan Q
FAU - Knuepfer, M M
AU  - Knuepfer MM
LA  - eng
GR  - DA 05180/DA/NIDA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - Netherlands
TA  - Brain Res
JT  - Brain research
JID - 0045503
RN  - 0 (Adrenergic beta-Antagonists)
RN  - 0 (Hormone Antagonists)
RN  - 0 (Peptide Fragments)
RN  - 0 (Receptors, Adrenergic)
RN  - 0 (Receptors, Corticotropin-Releasing Hormone)
RN  - 170809-51-5 (astressin)
RN  - 9015-71-8 (Corticotropin-Releasing Hormone)
RN  - 96118-75-1 (corticotropin releasing hormone (9-41))
RN  - 9Y8NXQ24VQ (Propranolol)
RN  - I5Y540LHVR (Cocaine)
SB  - IM
MH  - Adrenergic beta-Antagonists/administration & dosage
MH  - Animals
MH  - Cardiovascular System/drug effects
MH  - Central Nervous System/*metabolism
MH  - Cocaine/*administration & dosage
MH  - Corticotropin-Releasing Hormone/administration & dosage/antagonists & inhibitors
MH  - Drug Administration Schedule
MH  - Hemodynamics/*drug effects/physiology
MH  - Hormone Antagonists/administration & dosage
MH  - Male
MH  - Peptide Fragments/administration & dosage
MH  - Propranolol/administration & dosage
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, Adrenergic/*metabolism
MH  - Receptors, Corticotropin-Releasing Hormone/*metabolism
EDAT- 2001/02/27 10:00
MHDA- 2001/06/22 10:01
CRDT- 2001/02/27 10:00
PHST- 2001/02/27 10:00 [pubmed]
PHST- 2001/06/22 10:01 [medline]
PHST- 2001/02/27 10:00 [entrez]
AID - S0006-8993(00)03036-5 [pii]
AID - 10.1016/s0006-8993(00)03036-5 [doi]
PST - ppublish
SO  - Brain Res. 2001 Mar 2;893(1-2):1-10. doi: 10.1016/s0006-8993(00)03036-5.