Mesolimbic dopamine D2 receptor plasticity contributes to stress resilience in rats subjected to chronic mild stress

Abstract

RationaleFew studies have investigated neurobiological and biochemical differences between stress-resilient and stress-vulnerable experimental animals.ObjectivesWe investigated alterations in mesolimbic dopamine D2 receptor density and mRNA expression level in stressed rats at two time points, i.e. after 2 and 5 weeks of chronic mild stress (CMS).MethodsWe used the chronic mild stress paradigm because it is a well-established animal model of depression. Two groups of stressed rats were distinguished during CMS experiments: (1) stress reactive (70 %), which displayed a decrease in the drinking of a palatable sucrose solution during the stress regimen, and (2) stress resilient (30 %), which exhibited an unaltered drinking profile when compared with the unchallenged control group. [3H]Domperidone was used as a ligand to label dopamine D2 receptors, and a mixture of three specific oligonucleotides was used to evaluate dopamine D2 receptor mRNA changes in various regions of the rat brain.ResultsCMS strongly affected the mesolimbic dopamine circuit in stress-resilient group after 2 weeks and stress-reactive group of rats after 5 weeks which exhibited a decrease in the level of dopamine D2 receptor protein without alterations in D2 mRNA expression. Stress-resilient animals, but not stress-reactive animals, effectively adapted to the extended stress and coped with it. The increase in D2 mRNA expression returned the dopamine D2 receptor density to control levels in stress-resilient rats after 5 weeks of CMS, but not in stress-reactive animals.ConclusionsThese results clearly demonstrate that, despite earlier blunting, the activation of dopamine receptor biosynthesis in the dopamine mesoaccumbens system in stress-resilient rats is involved in active coping with stressful experiences, and it exhibits a delay in time.