PMID- 32971195
OWN - NLM
STAT- MEDLINE
DCOM- 20211109
LR  - 20211109
IS  - 1872-7549 (Electronic)
IS  - 0166-4328 (Linking)
VI  - 396
DP  - 2021 Jan 1
TI  - Lack of dopamine D4 receptor participation in mouse hyperdopaminergic locomotor 
      response.
PG  - 112925
LID - S0166-4328(20)30624-0 [pii]
LID - 10.1016/j.bbr.2020.112925 [doi]
AB  - Chronic methamphetamine (METH) treatment induces behavioral sensitization in 
      rodents. During this process, hyperactivation of the mesolimbic dopamine system 
      plays a central role, and dopamine D2-like receptor-based antipsychotics are 
      known to alleviate the behavioral hyperactivity. The atypical antipsychotic, 
      clozapine (Clz), acts partially as a dopamine D4 receptor (D4R) antagonist and 
      mitigates hyperdopaminergic drug addiction and/or comorbid psychotic symptoms; 
      however, it remains unclear whether D4R blockade contributes to the therapeutic 
      effects of Clz. Here, we evaluated the potential role of D4R in regulating 
      hyperdopaminergia-induced behavioral hyperactivity in METH behavioral 
      sensitization and dopamine transporter (DAT) knockdown (KD) mice. Clz or a 
      D4R-selective antagonist, L-745,870, were co-administered to mice with daily METH 
      in a METH sensitization model, and Clz or L-745,870 were administered alone in a 
      DAT KD hyperactivity model. Locomotor activity and accumbal D4R expression were 
      analyzed. Clz suppressed both the initiation and expression of METH behavioral 
      sensitization, as well as DAT KD hyperactivity. However, repetitive Clz treatment 
      induced tolerance to the suppression effect on METH sensitization initiation. In 
      contrast, D4R inhibition by L-745,870 had no effect on METH sensitization or DAT 
      KD hyperactivity. Accumbal D4R expression was similar between METH-sensitized 
      mice with and without Clz co-treatment. In sum, our results suggest the 
      mesolimbic D4R does not participate in behavioral sensitization encoded by 
      hyperdopaminergia, a finding which likely extends to the therapeutic effects of 
      Clz. Therefore, molecular targets other than D4R should be prioritized in the 
      development of future therapeutics for treatment of hyperdopaminergia-dependent 
      neuropsychiatric disorders.
CI  - Copyright (c) 2020 Elsevier B.V. All rights reserved.
FAU - Liao, I-Mei
AU  - Liao IM
AD  - Department of Physiology and Pharmacology, Graduate Institute of Biomedical 
      Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan; Department 
      of Neuroscience, Peter O'Donnell Jr. Brain Institute, University of Texas 
      Southwestern Medical Center, Dallas, TX, 75390-9111, United States.
FAU - Chen, Jin-Chung
AU  - Chen JC
AD  - Department of Physiology and Pharmacology, Graduate Institute of Biomedical 
      Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan; Chang Gung 
      Memorial Hospital, Keelung, Taiwan; Healthy Ageing Research Center, Chang Gung 
      University, Taoyuan, Taiwan; Neuroscience Research Center, Chang Gung Memorial 
      Hospital, Linkou, Taiwan. Electronic address: jinchen@mail.cgu.edu.tw.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200921
PL  - Netherlands
TA  - Behav Brain Res
JT  - Behavioural brain research
JID - 8004872
RN  - 0 (3-((4-(4-chlorophenyl)piperazin-1-yl)methyl)-1H-pyrrolo(2,3-b)pyridine)
RN  - 0 (Antipsychotic Agents)
RN  - 0 (Dopamine Agents)
RN  - 0 (Drd4 protein, mouse)
RN  - 0 (Pyridines)
RN  - 0 (Pyrroles)
RN  - 137750-34-6 (Receptors, Dopamine D4)
RN  - 44RAL3456C (Methamphetamine)
RN  - J60AR2IKIC (Clozapine)
SB  - IM
MH  - Amphetamine-Related Disorders/metabolism/physiopathology
MH  - Animals
MH  - Antipsychotic Agents/administration & dosage/*pharmacology
MH  - Behavior, Animal/drug effects
MH  - Central Nervous System Sensitization/*drug effects
MH  - Clozapine/administration & dosage/*pharmacology
MH  - Disease Models, Animal
MH  - Dopamine Agents/administration & dosage/*pharmacology
MH  - Locomotion/*drug effects
MH  - Methamphetamine/administration & dosage/*pharmacology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Inbred ICR
MH  - Mice, Knockout
MH  - Mice, Transgenic
MH  - Psychotic Disorders/metabolism/physiopathology
MH  - Pyridines/pharmacology
MH  - Pyrroles/pharmacology
MH  - Receptors, Dopamine D4/*antagonists & inhibitors
OTO - NOTNLM
OT  - Behavioral sensitization
OT  - Clozapine
OT  - Dopamine D4 receptor
OT  - Dopamine transporter
OT  - Methamphetamine addiction
OT  - Psychosis
EDAT- 2020/09/25 06:00
MHDA- 2021/11/10 06:00
CRDT- 2020/09/24 20:09
PHST- 2020/06/12 00:00 [received]
PHST- 2020/08/26 00:00 [revised]
PHST- 2020/09/17 00:00 [accepted]
PHST- 2020/09/25 06:00 [pubmed]
PHST- 2021/11/10 06:00 [medline]
PHST- 2020/09/24 20:09 [entrez]
AID - S0166-4328(20)30624-0 [pii]
AID - 10.1016/j.bbr.2020.112925 [doi]
PST - ppublish
SO  - Behav Brain Res. 2021 Jan 1;396:112925. doi: 10.1016/j.bbr.2020.112925. Epub 2020 
      Sep 21.