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

• Published in: Psychopharmacology Vol. 227; no. 4; pp. 583 - 593
• Main Authors: Żurawek, Dariusz, Faron-Górecka, Agata, Kuśmider, Maciej, Kolasa, Magdalena, Gruca, Piotr, Papp, Mariusz, Dziedzicka-Wasylewska, Marta
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer-Verlag 01.06.2013
• Subjects: Animals; Biomedical and Life Sciences; Biomedicine; Brain - metabolism; Depression - physiopathology; Disease Models, Animal; Domperidone - metabolism; Gene Expression Regulation; Male; Neurosciences; Original Investigation; Pharmacology/Toxicology; Psychiatry; Rats; Rats, Wistar; Receptors, Dopamine D2 - genetics; Receptors, Dopamine D2 - metabolism; RNA, Messenger - metabolism; Stress, Psychological - physiopathology; Sucrose - administration & dosage; Time Factors; Stress resilience; Domperidone; receptor; D; Rat; In situ hybridisation; Chronic mild stress; Depression; Dopamine mesolimbic system; mRNA
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s00213-013-2990-3

Rationale Few studies have investigated neurobiological and biochemical differences between stress-resilient and stress-vulnerable experimental animals. Objectives We investigated alterations in mesolimbic dopamine D 2 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). Methods We 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. [ 3 H]Domperidone was used as a ligand to label dopamine D 2 receptors, and a mixture of three specific oligonucleotides was used to evaluate dopamine D 2 receptor mRNA changes in various regions of the rat brain. Results CMS 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 D 2 receptor protein without alterations in D 2 mRNA expression. Stress-resilient animals, but not stress-reactive animals, effectively adapted to the extended stress and coped with it. The increase in D 2 mRNA expression returned the dopamine D 2 receptor density to control levels in stress-resilient rats after 5 weeks of CMS, but not in stress-reactive animals. Conclusions These 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.