Role of dopamine D2 receptors in plasticity of stress-induced addictive behaviours

Hye Ri Sim, Tae Yong Choi, Hyo Jin Lee, Eun Young Kang, Sehyoun Yoon, Pyung Lim Han, Se Young Choi, Ja Hyun Baik

Research output: Contribution to journalArticlepeer-review

56 Scopus citations

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 languageEnglish
Article number1579
JournalNature Communications
Volume4
DOIs
StatePublished - 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.

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