Schizophrenia-like disruptions of sensory gating by serotonin receptor stimulation in rats: Effect of MDMA, DOI and 8-OH-DPAT

作者：Thwaites Shane J; Gogos Andrea; Van den Buuse Maarten^*

来源：Pharmacology Biochemistry and Behavior, 2013, 112: 71-77.

DOI：10.1016/j.pbb.2013.09.016

• Sensory gating
• Schizophrenia
• MDMA
• DOI
• 8-OH-DPAT
• Ecstasy

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; 2.0 mg/kg), the 5-HT2A/2C receptor agonist, DOI (0.5 mg/kg), or the 5-HT1A/7 receptor agonist, 8-OH-DPAT (0.5 mg/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.

• 出版日期2013-11-1