BACKGROUND: Antagonists of the N-methyl-D-aspartate (NMDA) receptors induce a broad range of psychophysiologic symptoms in healthy subjects that are similar to those of schizophrenia, such as disturbances in the sensory gating of stimuli. Because antipsychotics reduce symptoms in schizophrenia, they may also reduce the effects of NMDA antagonists. METHODS: In our study, a group of 18 healthy male volunteers was tested in prepulse inhibition (PPI) and P50 evoked potential paradigms during placebo-placebo, placebo-ketamine (.3 mg/kg; intravenous), and 2-mg haloperidol/.3 mg/kg intravenous ketamine conditions. RESULTS:Suppression of PPI and P50 in the ketamine condition did not differ from either the placebo-placebo or the haloperidol-ketamine condition; however, a significant reduction in percentage PPI to the lowest prepulse intensity and a reduction of P50 suppression were found in the haloperidol-ketamine condition. CONCLUSIONS: The combination of haloperidol and ketamine was found to disrupt P50 suppression and PPI in healthy male volunteers, whereas ketamine alone did not affect either measure. This may imply that the disrupted P50 suppression and PPI found in schizophrenia is related to reduced dopaminergic activity, most likely in the prefrontal cortex.
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BACKGROUND: Antagonists of the N-methyl-D-aspartate (NMDA) receptors induce a broad range of psychophysiologic symptoms in healthy subjects that are similar to those of schizophrenia, such as disturbances in the sensory gating of stimuli. Because antipsychotics reduce symptoms in schizophrenia, they may also reduce the effects of NMDA antagonists. METHODS: In our study, a group of 18 healthy male volunteers was tested in prepulse inhibition (PPI) and P50 evoked potential paradigms during placebo-placebo, placebo-ketamine (.3 mg/kg; intravenous), and 2-mg haloperidol/.3 mg/kg intravenous ketamine conditions. RESULTS: Suppression of PPI and P50 in the ketamine condition did not differ from either the placebo-placebo or the haloperidol-ketamine condition; however, a significant reduction in percentage PPI to the lowest prepulse intensity and a reduction of P50 suppression were found in the haloperidol-ketamine condition. CONCLUSIONS: The combination of haloperidol and ketamine was found to disrupt P50 suppression and PPI in healthy male volunteers, whereas ketamine alone did not affect either measure. This may imply that the disrupted P50 suppression and PPI found in schizophrenia is related to reduced dopaminergic activity, most likely in the prefrontal cortex.
Authors: T B Halene; R S Ehrlichman; Y Liang; E P Christian; G J Jonak; T L Gur; J A Blendy; H C Dow; E S Brodkin; F Schneider; R C Gur; S J Siegel Journal: Genes Brain Behav Date: 2009-05-08 Impact factor: 3.449