5-HYDROXYTRYPTAMINE(2) RECEPTORS MODULATE AUDITORY FILTERING IN THE RAT

Sensory processing deficits are a hallmark of schizophrenia and can be demonstrated by recording auditory evoked potentials (AEPs) elicited in response to closely paired click stimuli. In nonschizophrenic human s, as well as in rats, the amplitude of the response to the second cli ck is reduced (filtered) compared with the first. In contrast, schizop hrenics, or rats treated with amphetamine, generate AEPs that have sma ller amplitudes and show little or no reduction in the response to the second click. We sought to evaluate the role of 5-hydroxytryptamine(2 ) 5-HT2 receptors in auditory filtering. Male Sprague-Dawley rats were implanted with a skull screw electrode to permit chronic recording of AEPs from a point approximating human vertex. During subsequent recor ding sessions, pairs of clicks (a conditioning click followed by a tes t click) were presented 500 msec apart. Parameters of N40, a dominant midlatency component of the AEP, were examined to evaluate the effects of a 5-HT2 receptor agonist, (+/-)-2,5-dimethoxy-4-iodoamphetamine (D OI), and a 5-HT2 receptor antagonist, ketanserin. Systemic administrat ion of ketanserin reduced sensory filtering in a dose-dependent manner . Conversely, DOI significantly improved filtering. In addition, DOI d ose-dependently antagonized the disruption of filtering induced by adm inistration of amphetamine (1.83 mg/kg i.p.). Taken together, these re sults indicate an important role for 5-HT2 receptors in the modulation of auditory filtering.