Corticotropin-releasing factor receptor blockade enhances conditioned aversive properties of cocaine in rats

The behavioral profile of corticotropin-releasing factor (CRF) in mediating anxiogenic-like and aversive responses to stressors may be particularly relevant for dependence and withdrawal in drug-experienced organisms. Moreover, stressful aspects of drug exposure in the drug naive organism may also i...

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Bibliographic Details
Published in:Psychopharmacologia 1998-04, Vol.136 (3), p.247-255
Main Authors: HEINRICHS, S. C, KLAASSEN, A, KOOB, G. F, SCHULTEIS, G, AHMED, S, DE SOUZA, E. B
Format: Article
Language:English
Subjects:
Animals
Aversion
Avoidance Learning - drug effects
Biological and medical sciences
Cocaine
Cocaine - pharmacology
Corticotropin-releasing hormone
Corticotropin-Releasing Hormone - analogs & derivatives
Corticotropin-Releasing Hormone - pharmacology
Dose-Response Relationship, Drug
Drug addictions
Drug self-administration
Drug Synergism
Injections, Intravenous
Injections, Intraventricular
Jugular Veins
Latency
Male
Medical sciences
Narcotics - pharmacology
Peptide Fragments - pharmacology
Rats
Rats, Wistar
Receptors, Corticotropin-Releasing Hormone - antagonists & inhibitors
Saccharin
Taste - drug effects
Toxicology
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Summary:The behavioral profile of corticotropin-releasing factor (CRF) in mediating anxiogenic-like and aversive responses to stressors may be particularly relevant for dependence and withdrawal in drug-experienced organisms. Moreover, stressful aspects of drug exposure in the drug naive organism may also induce CRF system activation. In the present studies, the dependence of aversive properties of cocaine on activation of endogenous CRF systems has been evaluated in rats using taste conditioning and runway self-administration paradigms. Systemic cocaine administration (20 mg/kg i.p.) produced a conditioned saccharin aversion which was dose-dependently potentiated by central administration of the CRF receptor antagonist, D-phe CRF (12 41). In addition, i.v. cocaine administration (0.75 mg/kg per injection i.v.) produced runway goal-box avoidance and conditioned place avoidance responses which were significantly accelerated by CRF antagonist treatment. In contrast, CRF receptor stimulation using CRF itself abolished cocaine-induced increases in goal latency in the runway paradigm. This generalized involvement of CRF systems in cocaine-related motivational/associative states is consistent with the comprehensive role of CRF in mediating emotional responses to non-drug stressors.
ISSN:0033-3158
1432-2072
DOI:10.1007/s002130050563