Escalated cocaine "binges" in rats: enduring effects of social defeat stress or intra-VTA CRF.
Psychopharmacology (Berl)
; 234(18): 2823-2836, 2017 Sep.
Article
de En
| MEDLINE
| ID: mdl-28725939
ABSTRACT
RATIONALE Exposure to intermittent social defeat stress elicits corticotropin releasing factor (CRF) release into the VTA and induces long-term modulation of mesocorticolimbic dopamine activity in rats. These adaptations are associated with an intense cocaine-taking phenotype, which is prevented by CRF receptor antagonists. OBJECTIVE:
The present studies examine whether infusion of CRF into the VTA is sufficient to escalate cocaine-taking behavior, in the absence of social defeat experience. Additionally, we aimed to characterize changes in cocaine valuation that may promote binge-like cocaine intake.METHODS:
Male Long-Evans rats were microinjected into the VTA with CRF (50 or 500 ng/side), vehicle, or subjected to social defeat stress, intermittently over 10 days. Animals were then trained to self-administer IV cocaine (FR5). Economic demand for cocaine was evaluated using a within-session behavioral-economics threshold procedure, which was followed by a 24-h extended access "binge."RESULTS:
Rats that experienced social defeat or received intra-VTA CRF microinfusions (50 ng) both took significantly more cocaine than controls over the 24-h binge but showed distinct patterns of intake. Behavioral economic analysis revealed that individual demand for cocaine strongly predicts binge-like consumption, and demand elasticity (i.e. α) is augmented by intra-VTA CRF, but not by social defeat. The effects of CRF on cocaine-taking were also prevented by intra-VTA pretreatment with CP376395, but not Astressin-2B.CONCLUSIONS:
Repeated infusion of CRF into the VTA persistently alters cocaine valuation and intensifies binge-like drug intake in a CRF-R1-dependent manner. Conversely, the persistent pattern of cocaine bingeing induced by social defeat stress may suggest impaired inhibitory control, independent of reward valuation.Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Stress psychologique
/
Corticolibérine
/
Cocaïne
/
Aire tegmentale ventrale
/
Troubles liés à la cocaïne
Type d'étude:
Prognostic_studies
Limites:
Animals
Langue:
En
Journal:
Psychopharmacology (Berl)
Année:
2017
Type de document:
Article
Pays d'affiliation:
États-Unis d'Amérique