title: Schizophrenia-like disruptions of sensory gating by serotonin receptor stimulation in rats: effect of MDMA, DOI and 8-OH-DPAT.
abstract: Schizophrenia pathophysiology is associated with alterations in several neurotransmitter systems, particularly dopamine, glutamate and serotonin (5-HT). Schizophrenia patients also have disruptions in sensory gating, a brain information filtering mechanism in response to repeated sensory stimuli. Dopamine and glutamate have been implicated in sensory gating; however, little is known about the contribution of serotonin. We therefore investigated the effects of several psychoactive compounds that alter serotonergic neuronal activity on event-related potentials (ERP) to paired auditory pulses. Male Sprague-Dawley rats were implanted with cortical surface electrodes to measure ERPs to 150 presentations of two 85 dB bursts of white noise, 500 ms apart (S1 and S2). Saline-treated animals suppressed the response to S2 to less than 50% of S1. In contrast, treatment with the serotonin releaser, MDMA (ecstasy; 2.0mg/kg), the 5-HT2A/2C receptor agonist, DOI (0.5mg/kg), or the 5-HT1A/7 receptor agonist, 8-OH-DPAT (0.5mg/kg), caused an increase in S2/S1 ratios. Analysis of waveform components suggested that the S2/S1 ratio disruption by MDMA was due to subtle effects on the ERPs to S1 and S2; DOI caused the disruption primarily by reducing the ERP to S1; 8-OH-DPAT-induced disruptions were due to an increase in the ERP to S2. These results show that 5-HT receptor stimulation alters S2/S1 ERP ratios in rats. These results may help to elucidate the sensory gating deficits observed in schizophrenia patients.
authors.affiliation: Behavioural Neuroscience Laboratory, Florey Institute of Neuroscience and Mental Health, Melbourne, Australia; Department of Pharmacology, University of Melbourne, Australia.
authors.forename: Shane J
authors.initials: SJ
authors.lastname: Thwaites
authors.forename: Andrea
authors.initials: A
authors.lastname: Gogos
authors.forename: Maarten
authors.initials: M
authors.lastname: Van den Buuse
mesh_terms: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology*; D000662:Amphetamines / Q000494:pharmacology*; D000818:Animals; D005071:Evoked Potentials / Q000187:drug effects; D008297:Male; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D012559:Schizophrenia / Q000503:physiopathology*; D055139:Sensory Gating / Q000187:drug effects*
chemical_list: D000662:Amphetamines; D011985:Receptors, Serotonin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D018817:N-Methyl-3,4-methylenedioxyamphetamine; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine
keywords: 8-OH-DPAT; DOI; Ecstasy; MDMA; Schizophrenia; Sensory gating