PMID- 33031912
OWN - NLM
STAT- MEDLINE
DCOM- 20210927
LR  - 20210927
IS  - 1095-9564 (Electronic)
IS  - 1074-7427 (Linking)
VI  - 176
DP  - 2020 Dec
TI  - The role of dopamine D1 receptors in MDMA-induced memory impairments.
PG  - 107322
LID - S1074-7427(20)30166-0 [pii]
LID - 10.1016/j.nlm.2020.107322 [doi]
AB  - (+/-) 3,4-Methylenedioxymethamphetamine (MDMA) is a recreationally abused 
      psychostimulant that impairs memory performance. This effect is often attributed 
      to a working memory impairment resulting from compromised serotonin systems. 
      However, recent evidence from non-human animal experimental studies suggests that 
      acute MDMA may indirectly impair memory performance through overstimulation of 
      dopamine (DA) D1 receptors, which increases perseverative responding during 
      memory tasks. This hypothesis was explored using DA D1 mutant (DAD1(-/-)) rats 
      which possess a selective down-regulation in functional D1 receptors. Adult male 
      Wistar DAD1(-/-) rats and wild type controls were trained over 25 sessions on a 
      spatial working memory T-maze delayed non-matching to position (DNMTP) task. Once 
      trained, the rats were administered MDMA (1.5, 2.25 and 3 mg/kg) or saline 
      fifteen minutes prior to testing on DNMTP with all subjects experiencing all drug 
      doses and saline three times. We predicted that controls would demonstrate 
      decreased task accuracy following MDMA, driven by an increase in perseverative 
      errors. In contrast, we predicted that DAD1(-/-) rats would be protected from 
      MDMA-induced perseverative errors due to their reduced D1 receptor function. As 
      predicted, during the third block of MDMA administration, control rats 
      demonstrated decreased task accuracy following 2.25 and 3 mg/kg doses, driven by 
      an increase in perseverative errors. In addition, DAD1(-/-) rats were protected 
      from MDMA-induced task deficits. These findings challenge the assumption that 
      MDMA's acute effects on memory performance are predominantly due to serotonergic 
      mechanisms and provide support for the hypothesis that acute MDMA impairs memory 
      performance in rats via overstimulation of D1 receptors by increasing 
      perseverative behaviour.
CI  - Copyright (c) 2020 Elsevier Inc. All rights reserved.
FAU - Squire, Hanna
AU  - Squire H
AD  - School of Psychology, Victoria University of Wellington, PO Box 600, Wellington, 
      New Zealand.
FAU - Youn, Jiun
AU  - Youn J
AD  - School of Psychology, Victoria University of Wellington, PO Box 600, Wellington, 
      New Zealand.
FAU - Ellenbroek, Bart A
AU  - Ellenbroek BA
AD  - School of Psychology, Victoria University of Wellington, PO Box 600, Wellington, 
      New Zealand. Electronic address: bart.ellenbroek@vuw.ac.nz.
FAU - Harper, David N
AU  - Harper DN
AD  - School of Psychology, Victoria University of Wellington, PO Box 600, Wellington, 
      New Zealand.
LA  - eng
PT  - Journal Article
DEP - 20201006
PL  - United States
TA  - Neurobiol Learn Mem
JT  - Neurobiology of learning and memory
JID - 9508166
RN  - 0 (Receptors, Dopamine D1)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
SB  - IM
MH  - Animals
MH  - Male
MH  - Memory Disorders/*chemically induced
MH  - Memory, Short-Term/*drug effects
MH  - Mice, Knockout
MH  - N-Methyl-3,4-methylenedioxyamphetamine/administration & dosage/*toxicity
MH  - Rats
MH  - Rats, Wistar
MH  - Receptors, Dopamine D1/*agonists/genetics/physiology
OTO - NOTNLM
OT  - D1 receptors
OT  - Dopamine
OT  - MDMA
OT  - Memory performance
OT  - Perseveration
OT  - Rats
EDAT- 2020/10/09 06:00
MHDA- 2021/09/28 06:00
CRDT- 2020/10/08 20:10
PHST- 2020/05/18 00:00 [received]
PHST- 2020/09/15 00:00 [revised]
PHST- 2020/09/30 00:00 [accepted]
PHST- 2020/10/09 06:00 [pubmed]
PHST- 2021/09/28 06:00 [medline]
PHST- 2020/10/08 20:10 [entrez]
AID - S1074-7427(20)30166-0 [pii]
AID - 10.1016/j.nlm.2020.107322 [doi]
PST - ppublish
SO  - Neurobiol Learn Mem. 2020 Dec;176:107322. doi: 10.1016/j.nlm.2020.107322. Epub 
      2020 Oct 6.