Central corticotropin releasing factor (CRF) and adrenergic receptors mediate hemodynamic responses to cocaine

Hongwei Dong, Qi Gan, Mark M. Knuepfer

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

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 α-helical CRF9-41 (10 μg/5 μl, icv) prevented the decrease in cardiac output in vascular responders without altering hemodynamic responses to cocaine in mixed responders. Astressin (5 μg/5 μl, icv) exerted a similar effect in vascular responders. The α2 receptor antagonist, yohimbine (3 μg/μl, icv) also prevented the decrease in cardiac output in vascular responders. Lower doses of α-helical CRF9-41 (1 and 3 μg) were ineffective whereas higher doses of either CRF antagonist were lethal within 24 h. In contrast, propranolol (3 or 30 μg, 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 β-adrenoceptors may be responsible for the reported effects of intravenous propranolol on cocaine-induced responses.

Original languageEnglish (US)
Pages (from-to)1-10
Number of pages10
JournalBrain Research
Volume893
Issue number1-2
DOIs
StatePublished - Mar 2 2001

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Corticotropin-Releasing Hormone Receptors
Cocaine
Cardiac Output
Adrenergic Receptors
Hemodynamics
Blood Vessels
Corticotropin-Releasing Hormone
Vascular Resistance
Propranolol
Yohimbine
Intravenous Administration
Arterial Pressure
Pharmaceutical Preparations

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

Cite this

Central corticotropin releasing factor (CRF) and adrenergic receptors mediate hemodynamic responses to cocaine. / Dong, Hongwei; Gan, Qi; Knuepfer, Mark M.

In: Brain Research, Vol. 893, No. 1-2, 02.03.2001, p. 1-10.

Research output: Contribution to journalArticle

Dong, Hongwei ; Gan, Qi ; Knuepfer, Mark M. / Central corticotropin releasing factor (CRF) and adrenergic receptors mediate hemodynamic responses to cocaine. In: Brain Research. 2001 ; Vol. 893, No. 1-2. pp. 1-10.
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