title: Role of dopamine D2 receptors in plasticity of stress-induced addictive behaviours.
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.
authors.affiliation: Molecular Neurobiology Laboratory, School of Life Sciences and Biotechnology, Korea University, Seoul 136-701, South Korea.
authors.forename: Hye-Ri
authors.initials: HR
authors.lastname: Sim
authors.forename: Tae-Yong
authors.initials: TY
authors.lastname: Choi
authors.forename: Hyo Jin
authors.initials: HJ
authors.lastname: Lee
authors.forename: Eun Young
authors.initials: EY
authors.lastname: Kang
authors.forename: Sehyoun
authors.initials: S
authors.lastname: Yoon
authors.forename: Pyung-Lim
authors.initials: PL
authors.lastname: Han
authors.forename: Se-Young
authors.initials: SY
authors.lastname: Choi
authors.forename: Ja-Hyun
authors.initials: JH
authors.lastname: Baik
mesh_terms: D000818:Animals; D001007:Anxiety / Q000150:complications / Q000378:metabolism / Q000503:physiopathology; D016739:Behavior, Addictive / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology*; D001522:Behavior, Animal / Q000187:drug effects; D059333:Central Nervous System Sensitization / Q000187:drug effects; D003042:Cocaine / Q000494:pharmacology; D003213:Conditioning, Psychological / Q000187:drug effects; D004558:Electric Stimulation; D055785:Gene Knockdown Techniques; D066298:In Vitro Techniques; D016086:Lentivirus / Q000378:metabolism; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D009473:Neuronal Plasticity / Q000187:drug effects; D009714:Nucleus Accumbens / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D017448:Receptors, Dopamine D2 / Q000172:deficiency / Q000378:metabolism*; D012149:Restraint, Physical; D013315:Stress, Psychological / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology*
chemical_list: D017448:Receptors, Dopamine D2; D003042:Cocaine