Role of Hypothalamic-Pituitary-Adrenal axis and corticotropin-releasing factor stress system on cue-induced relapse to alcohol seeking.
A large body of evidence has shown that the Corticotropin Releasing Factor (CRF) system, which plays a key role in stress modulation, is deeply involved in relapse to alcohol seeking induced by exposure to stressful events such as foot shock or yohimbine injections. Exposure to environmental cues is also known to be a trigger for alcohol relapse, nevertheless, the relationship between the relapse evoked by the cue-induced model and the CRF stress systems remains unclear. The purpose of this study was to evaluate, in male Wistar rats, the involvement of the CRF system and Hypothalamic-Pituitary-Adrenal (HPA) axis in relapse induced by environmental cues. Antalarmin, a selective CRF1 receptor antagonist, Metyrapone, a corticosterone (CORT) synthesis inhibitor and CORT were evaluated for their effects on the reinstatement test in a cue-induced relapse model. Antalarmin (20mg/kg) blocked relapse to alcohol seeking induced by environmental cues. Metyrapone (50 and 100mg/kg) also blocked relapse in Wistar rats but only at the highest dose (100mg/kg). Corticosterone had no effect on relapse at the doses tested. The results obtained from this study suggest that the CRF stress system and the HPA axis are involved in cue-induced alcohol relapse.
Universidade de São Paulo, Instituto de Psicologia, Departamento de Psicologia Experimental, Sao Paulo, SP, Brazil.
Fernanda L
FL
Galesi
School of Pharmacy, Pharmacology Unit, University of Camerino, Camerino, MC 62032, Italy.
Lydia O
LO
Ayanwuyi
Universidade de São Paulo, Instituto de Psicologia, Departamento de Psicologia Experimental, Sao Paulo, SP, Brazil.
Miriam Garcia
MG
Mijares
School of Pharmacy, Pharmacology Unit, University of Camerino, Camerino, MC 62032, Italy.
Andrea
A
Cippitelli
School of Pharmacy, Pharmacology Unit, University of Camerino, Camerino, MC 62032, Italy.
Nazzareno
N
Cannella
School of Pharmacy, Pharmacology Unit, University of Camerino, Camerino, MC 62032, Italy.
Roberto
R
Ciccocioppo
School of Pharmacy, Pharmacology Unit, University of Camerino, Camerino, MC 62032, Italy. Electronic address: massimo.ubaldi@unicam.it.
Massimo
M
Ubaldi
D000818:Animals; D016739:Behavior, Addictive / Q000503:physiopathology*; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism*; D003463:Cues; D000431:Ethanol / Q000494:pharmacology*; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000503:physiopathology*; D008297:Male; D008797:Metyrapone / Q000494:pharmacology; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors; D012008:Recurrence; D013312:Stress, Physiological / Q000187:drug effects*; D000099052:CRF Receptor, Type 1
D018019:Receptors, Corticotropin-Releasing Hormone; D000431:Ethanol; D000099052:CRF Receptor, Type 1; D003346:Corticotropin-Releasing Hormone; D008797:Metyrapone
Addiction; Alcohol; CRF; Reinstatement; Relapse; Stress