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

Abstract:

: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.

journal_title

Psychopharmacology

authors

Heinrichs SC,Klaassen A,Koob GF,Schulteis G,Ahmed S,De Souza EB

doi

10.1007/s002130050563

subject

Has Abstract

pub_date

1998-04-01 00:00:00

pages

247-55

issue

3

eissn

0033-3158

issn

1432-2072

journal_volume

136

pub_type

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