Abstract
Dopaminergic systems are implicated in stress-related behaviour. Here we investigate behavioural responses to chronic stress in dopamine D2 receptor knockout mice and find that anxiety-like behaviours are increased compared with wild-type mice. Repeated stress exposure suppresses cocaine-induced behavioural sensitization, cocaine-seeking and relapse behaviours in dopamine D2 receptor knockout mice. Cocaine challenge after drug withdrawal in cocaine-experienced wild-type or dopamine D2 receptor knockout mice is associated with inhibition of long-term depression in the nucleus accumbens, and chronic stress during withdrawal prevents inhibition after cocaine challenge in cocaine-experienced dopamine D2 receptor knockout mice, but not in wild-type mice. Lentiviral-induced knockdown of dopamine D2 receptors in the nucleus accumbens of wild-type mice does not affect basal locomotor activity, but confers stress-induced inhibition of the expression of cocaine-induced behavioural sensitization. Stressed mice depleted of dopamine D2 receptors do not manifest long-term depression inhibition. Our results suggest that dopamine D2 receptors have roles in regulating synaptic modification triggered by stress and drug addiction.
| Original language | English |
|---|---|
| Article number | 1579 |
| Journal | Nature Communications |
| Volume | 4 |
| DOIs | |
| State | Published - 2013 |
Bibliographical note
Funding Information:We thank members of our laboratories for help and discussion. This work was supported by research grants (to J.-H.B.; numbers 2012K001117, 2011K000273, 2010K000814 and 2009K001254) from the Brain Research Center of the 21st Century Frontier Research Program, and Basic Science Research Program (to J.-H.B.; 2011-0027320) and MRC Program (to S.-Y.C.; 2010-0029510) through the National Research Foundation of Korea (NRF) funded by the Research Program of the Korean Ministry of Science and Technology, and by a grant of the Korean Health Technology R&D Project (to J.-H.B.; A111776) from the Ministry of Health and Welfare, Republic of Korea. H.S., H.J.L., E.Y K. and S.Y were the recipients of a Brain Korea 21 Program Grant from the Korean Ministry of Education. S.Y. was supported by a Hi Seoul Science (Humanities) Fellowship from the Seoul Scholarship Foundation.