Naloxone-induced conditioned place aversion score and extinction period are higher in C57BL/6J morphine-dependent mice than in Swiss: Role of HPA axis

• Published in: Pharmacology, biochemistry and behavior Vol. 201; p. 173106
• Main Authors: Navarro-Zaragoza, Javier, Martínez-Laorden, E., Teruel-Fernández, F. Javier, Gómez-Murcia, Victoria, Cánovas, Alberto, Milanés, María-Victoria, Laorden, María-Luisa, Almela, Pilar
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-02-2021
• Subjects: Aversive memory; CPA expression; CPA extinction; HPA axis; Morphine withdrawal; HPA axis; Morphine withdrawal; CPA extinction; CPA expression; Aversive memory
• ISSN: 0091-3057; 1873-5177
• DOI: 10.1016/j.pbb.2021.173106

Intense associative memories develop between drug-paired contextual cues and the drug withdrawal associated aversive feeling. They have been suggested to contribute to the high rate of relapse. Our study was aimed to elucidate the involvement of hypothalamic-pituitary-adrenocortical (HPA) axis activity in the expression and extinction of aversive memory in Swiss and C57BL/6J (B6) mice. The animals were rendered dependent on morphine by i.p. injection of increasing doses of morphine (10–60 mg/kg). The negative state associated with naloxone (1 mg/kg s.c.) precipitated morphine withdrawal was examined by using conditioned place aversion (CPA) paradigm. B6 mice obtained a higher aversion score and took longer to extinguish the aversive memory than Swiss mice. In addition, corticosterone levels were increased after CPA expression. Moreover, corticosterone levels were decreased during CPA extinction in Swiss mice without changes in B6 mice. Pre-treatment with the selective CRF1 receptor antagonist CP-154,526 before naloxone, impaired morphine-withdrawal aversive memory acquisition and decreased the extinction period. CP-154,526 also antagonized the increased levels of corticosterone observed after CPA expression in Swiss mice, without any changes in B6 mice. These results indicate that HPA axis could be a critical factor governing opioid withdrawal memory storage and retrieval, but in a strain or stock-specific manner. The differences observed between Swiss and B6 mice suggest that the treatment of addictive disorders should consider different individual predisposition to associate the aversive learning with the context.
•First study to specifically investigate HPA axis in two different strains of mice•B6 mice showed higher CPA expression than Swiss strain.•B6 mice showed longer period of extinction of the aversive memory than Swiss.