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Pharmacological Mechanisms Involved in Sensory Gating Disruption Induced by (±)-3,4-Methylene- Dioxymethamphetamine (MDMA): Relevance to Schizophrenia

1
Florey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne 3010, Australia
2
School of Psychology and Public Health, La Trobe University, Melbourne 3086, Australia
*
Author to whom correspondence should be addressed.
Brain Sci. 2020, 10(1), 44; https://doi.org/10.3390/brainsci10010044
Received: 6 November 2019 / Revised: 26 December 2019 / Accepted: 10 January 2020 / Published: 13 January 2020
(This article belongs to the Section Systems Neuroscience)
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. View Full-Text
Keywords: sensory gating; MDMA; ecstasy; dopamine; serotonin; schizophrenia sensory gating; MDMA; ecstasy; dopamine; serotonin; schizophrenia
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Lee, J.; Thwaites, S.; Gogos, A.; van den Buuse, M. Pharmacological Mechanisms Involved in Sensory Gating Disruption Induced by (±)-3,4-Methylene- Dioxymethamphetamine (MDMA): Relevance to Schizophrenia. Brain Sci. 2020, 10, 44.

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