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Updated: Aug 26, 2026

The Unpredictable Chronic Mild Stress Protocol for Inducing Anhedonia in Mice
Published on: October 24, 2018
An endogenous opiate mechanism seems to be involved in stress-induced anhedonia
1Departamento de Farmacología, Universidad Nacional de Córdoba, Argentina.
Abstract:
This study assessed the effect of an uncontrollable stressor on the preference for a palatable solution (sucrose 1%), and on the preference for a context associated with a single administration of D-amphetamine (3 mg/kg i.p.) by means of the conditioning place preference test. We also evaluated the effect of prior naloxone (2 mg/kg, i.p.) administration on the influence of this stressful stimulus in both tests. Animals previously submitted to a 120-min--but not 60-min--restraint period showed a selective reduction in the preference for sucrose intake as compared to unstressed animals. Similarly, an identical restraint exposure elicited a diminished preference for the place previously paired with amphetamine. Both stress-induced effects were blocked by prior naloxone administration. These data demonstrate that a highly aversive experience decreased the reinforcing efficacy of sucrose and amphetamine, suggesting that uncontrollable stress may lead to an impaired capacity to experience pleasure, which could resemble the anhedonia observed in clinical depression. Furthermore, an endogenous opiate mechanism activated by stress seems to be involved in stress-induced anhedonia since naloxone normalized the reduction of the rewarding induced by both reinforcers.
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