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 85dB bursts of white noise, 500ms 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. [Copyright &y& Elsevier]