PMID- 31941052
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200928
IS  - 2076-3425 (Print)
IS  - 2076-3425 (Electronic)
IS  - 2076-3425 (Linking)
VI  - 10
IP  - 1
DP  - 2020 Jan 13
TI  - Pharmacological Mechanisms Involved in Sensory Gating Disruption Induced by 
      (+/-)-3,4-Methylene- Dioxymethamphetamine (MDMA): Relevance to Schizophrenia.
LID - 10.3390/brainsci10010044 [doi]
LID - 44
AB  - Sensory gating deficits have been demonstrated in schizophrenia, but the 
      mechanisms involved remain unclear. In the present study, we used disruption of 
      paired-pulse gating of evoked potentials in rats by the administration of 
      (+/-)-3,4-methylene-dioxymethamphetamine (MDMA) to study serotonergic and 
      dopaminergic mechanisms involved in auditory sensory gating deficits. Male 
      Sprague-Dawley rats were instrumented with cortical surface electrodes to record 
      evoked potential changes in response to pairs of 85dB tones (S1 and S2), 500msec 
      apart. Administration of MDMA eliminated the normal reduction in the amplitude of 
      S2 compared to S1, representing disruption of auditory sensory gating. 
      Pretreatment of the animals with the dopamine D1 receptor antagonist, SCH23390, 
      the dopamine D2 receptor antagonist, haloperidol, the serotonin (5-HT)1A receptor 
      antagonist, WAY100635, or the 5-HT2A receptor antagonist, ketanserin, all blocked 
      the effect of MDMA, although the drugs differentially affected the individual S1 
      and S2 amplitudes. These data show involvement of both dopaminergic and 
      serotonergic mechanisms in disruption of auditory sensory gating by MDMA. These 
      and previous results suggest that MDMA targets serotonergic pathways, involving 
      both 5-HT1A and 5-HT2A receptors, leading to dopaminergic activation, involving 
      both D1 and D2 receptors, and ultimately sensory gating deficits. It is 
      speculated that similar interactive mechanisms are affected in schizophrenia.
FAU - Lee, Jaime
AU  - Lee J
AD  - Florey Institute of Neuroscience and Mental Health, University of Melbourne, 
      Melbourne 3010, Australia.
FAU - Thwaites, Shane
AU  - Thwaites S
AD  - Florey Institute of Neuroscience and Mental Health, University of Melbourne, 
      Melbourne 3010, Australia.
FAU - Gogos, Andrea
AU  - Gogos A
AD  - Florey Institute of Neuroscience and Mental Health, University of Melbourne, 
      Melbourne 3010, Australia.
FAU - van den Buuse, Maarten
AU  - van den Buuse M
AUID- ORCID: 0000-0002-7555-3799
AD  - Florey Institute of Neuroscience and Mental Health, University of Melbourne, 
      Melbourne 3010, Australia.
AD  - School of Psychology and Public Health, La Trobe University, Melbourne 3086, 
      Australia.
LA  - eng
GR  - Senior Research Fellowship/National Health and Medical Research Council/
GR  - DECRA/Australian Research Council/
PT  - Journal Article
DEP - 20200113
PL  - Switzerland
TA  - Brain Sci
JT  - Brain sciences
JID - 101598646
PMC - PMC7016806
OTO - NOTNLM
OT  - MDMA
OT  - dopamine
OT  - ecstasy
OT  - schizophrenia
OT  - sensory gating
OT  - serotonin
COIS- The authors do not have any conflicts of interest to report.
EDAT- 2020/01/17 06:00
MHDA- 2020/01/17 06:01
PMCR- 2020/01/01
CRDT- 2020/01/17 06:00
PHST- 2019/11/06 00:00 [received]
PHST- 2019/12/26 00:00 [revised]
PHST- 2020/01/10 00:00 [accepted]
PHST- 2020/01/17 06:00 [entrez]
PHST- 2020/01/17 06:00 [pubmed]
PHST- 2020/01/17 06:01 [medline]
PHST- 2020/01/01 00:00 [pmc-release]
AID - brainsci10010044 [pii]
AID - brainsci-10-00044 [pii]
AID - 10.3390/brainsci10010044 [doi]
PST - epublish
SO  - Brain Sci. 2020 Jan 13;10(1):44. doi: 10.3390/brainsci10010044.