Abstract
ceived one dose of MK801 (0.05, 0.1 or 0.5 mg/kg) and saline in a counterbalanced design (l week between tests). Thirty minutes after injection, animals were exposed to 5 minutes background noise (70 dB) followed by 5 types of startle stimuli (total of 111 trials): startle pulse alone (PA, 116 dB, 30 msec duration), and PA preceded by inhibitory prepulses (75, 80, or 85 dB, 30 msec duration), or by a facilitatory prepulse (73 dB, 10 msec duration). Baseline startle, percent inhibition/facilitation, and within session habituation were calculated. Complete disruption of PPI for all inhibitory trials occurred at the two higher doses of MK-801. Baseline amplitude and PPF were enhanced by low-dnse MK-801 but reduced by higher doses, and habituation of ASR was impaired by the higher doses. These findings further support the involvement of PCP or NMDA receptors in the modulation of sensory gating and suggest that unique sensory gating abnormalities result from NMDA antagonists and DA agonists. Similar patterns, if present in subgroups of schizophrenia patients, would provide indirect evidence for DA hyperactivity vs. hypoglutamatergia. Such differentiation could further our understanding of the pathophysiology and treatment resl:xmse of schizophrenic patients. (Supported by MH00859.)
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