Dopamine D1 and D3 Receptors Modulate Heroin-Induced Cognitive Impairment through Opponent Actions in Mice.
Chronic abuse of heroin leads to long-lasting and complicated cognitive impairment. Dopamine receptors are critically involved in the impulsive drug-driven behavior and the altered attention, processing speed, and mental flexibility that are associated with higher relapse rates. However, the effects of the different dopamine receptors and their possible involvement in heroin-induced cognitive impairment remain unclear.



The 5-choice serial reaction time task was used to investigate the profiles of heroin-induced cognitive impairment in mice. The expression levels of dopamine D1- and D2-like receptors in the prefrontal cortex, nucleus accumbens, and caudate-putamen were determined. The effects of dopamine receptors on heroin-induced impulsivity in the 5-choice serial reaction time task were examined by agonist/antagonist treatment on D1 or D3 receptor mutant mice.



Systemic heroin administration influences several variables in the 5-choice serial reaction time task, most notably premature responses, a measure of motor impulsivity. These behavioral impairments are associated with increased D1 receptor and decreased D3 receptor mRNA and protein levels in 3 observed brain areas. The heroin-evoked increase in premature responses is mimicked by a D1 agonist and prevented by a D1 antagonist or genetic ablation of the D1 receptor gene. In contrast, a D3 agonist decreases both basal and heroin-evoked premature responses, while genetic ablation of the D3 receptor gene results in increased basal and heroin-evoked premature responses.



Heroin-induced impulsive behavior in the 5-choice serial reaction time task is oppositely modulated by D1 and D3 receptor activation. The D1 receptors in the cortical-mesolimbic region play an indispensable role in modulating such behaviors.
College of Forensic Science, Xi'an Jiaotong University, Xi'an, Shaanxi, China; Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi'an, Shaanxi, China.
Yongsheng
Y
Zhu
College of Forensic Science, Xi'an Jiaotong University, Xi'an, Shaanxi, China; Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi'an, Shaanxi, China.
Yunpeng
Y
Wang
College of Forensic Science, Xi'an Jiaotong University, Xi'an, Shaanxi, China; Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi'an, Shaanxi, China.
Jianghua
J
Lai
College of Forensic Science, Xi'an Jiaotong University, Xi'an, Shaanxi, China; Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi'an, Shaanxi, China.
Shuguang
S
Wei
College of Forensic Science, Xi'an Jiaotong University, Xi'an, Shaanxi, China; Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi'an, Shaanxi, China.
Hongbo
H
Zhang
College of Forensic Science, Xi'an Jiaotong University, Xi'an, Shaanxi, China; Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi'an, Shaanxi, China.
Peng
P
Yan
College of Forensic Science, Xi'an Jiaotong University, Xi'an, Shaanxi, China; Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi'an, Shaanxi, China.
Yunxiao
Y
Li
College of Forensic Science, Xi'an Jiaotong University, Xi'an, Shaanxi, China; Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi'an, Shaanxi, China.
Xiaomeng
X
Qiao
College of Forensic Science, Xi'an Jiaotong University, Xi'an, Shaanxi, China; Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi'an, Shaanxi, China.
Fangyuan
F
Yin
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001552:Benzazepines / Q000494:pharmacology; D001578:Benzopyrans / Q000494:pharmacology; D060825:Cognitive Dysfunction / Q000139:chemically induced* / Q000503:physiopathology*; D003932:Heroin; D007175:Impulsive Behavior / Q000187:drug effects*; D008297:Male; D051379:Mice; D009154:Mutation; D017072:Neostriatum / Q000378:metabolism; D009714:Nucleus Accumbens; D010078:Oxazines / Q000494:pharmacology; D017397:Prefrontal Cortex / Q000378:metabolism; D011930:Reaction Time / Q000187:drug effects; D017447:Receptors, Dopamine D1 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000502:physiology*; D017448:Receptors, Dopamine D2 / Q000096:biosynthesis; D050637:Receptors, Dopamine D3 / Q000819:agonists / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology*
D000906:Antibodies; D001552:Benzazepines; D001578:Benzopyrans; D010078:Oxazines; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; C534628:SCH 23390; C062458:3,4,4a,10b-tetrahydro-4-propyl-2H,5H-(1)benzopyrano(4,3-b)-1,4-oxazin-9-ol; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D003932:Heroin
cognition; dopamine receptor; heroin; impulsivity