Brain corticotropin-releasing factor mediates 'anxiety-like' behavior induced by cocaine withdrawal in rats

Zoltán Sarnyai, Éva Bíró, J. Gardi, M. Vecsernyés, J. Julesz, G. Telegdy

Research output: Contribution to journalArticle

217 Citations (Scopus)

Abstract

Anxiety is a key symptom of the cocaine withdrawal syndrome in human addicts, and it is considered to be one of the major factors in precipitating relapse to chronic cocaine abuse. Corticotropin-releasing factor (CRF) plays an important role in the pathophysiology of anxiety and depression, and it may also be involved in the acute behavioral and neuroendocrine actions of cocaine. The role of endogenous CRF in cocaine withdrawal-induced anxiety was investigated in the present study. Animals were subjected to chronic cocaine (20 mg/kg, intraperitoneally, once a day for 14 days) administration. Rats tested 30 min after the last cocaine injection did not show withdrawal anxiety on the elevated plus maze or any alterations in brain CRF levels. Withdrawal (48 h) from chronic cocaine administration produced an intense anxiety-like behavior characterized by decreased open arm exploration. Immunoreactive CRF (CRF-LI) levels were selectively altered in the hypothalamus, in the amygdala and in the basal forebrain structures at the time of the behavioral anxiety, reflecting an increased activity of brain CRF systems. Daily intracerebroventricular (i.c.v.) pretreatment with an immunoserum raised against CRF completely prevented the development of anxiety induced by cocaine withdrawal. These data suggest that extrahypothalamic-limbic CRF hypersecretion may be involved in the development of anxiety related to cocaine withdrawal and that the CRF system may be a useful target for new pharmacotherapies for cocaine withdrawal and relapse.

Original languageEnglish
Pages (from-to)89-97
Number of pages9
JournalBrain Research
Volume675
Issue number1-2
DOIs
Publication statusPublished - Mar 27 1995

Fingerprint

Corticotropin-Releasing Hormone
Cocaine
Anxiety
Brain
Recurrence
Precipitating Factors
Cocaine-Related Disorders
Substance Withdrawal Syndrome
Amygdala
Hypothalamus
Depression
Drug Therapy
Injections

Keywords

  • Anxiety
  • Cocaine withdrawal
  • Corticotropin-releasing factor
  • Plus maze

ASJC Scopus subject areas

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

Cite this

Brain corticotropin-releasing factor mediates 'anxiety-like' behavior induced by cocaine withdrawal in rats. / Sarnyai, Zoltán; Bíró, Éva; Gardi, J.; Vecsernyés, M.; Julesz, J.; Telegdy, G.

In: Brain Research, Vol. 675, No. 1-2, 27.03.1995, p. 89-97.

Research output: Contribution to journalArticle

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