Effects of phencyclidine (PCP) and MK 801 on the EEGq in the prefrontal cortex of conscious rats; antagonism by clozapine, and antagonists of AMPA-, α_1- and 5-HT_(2A)-receptors

摘要

1 The electroencephalographic (EEG) effects of the propsychotic agent phencyclidine (PCP), were studied in conscious rats using power spectra (0-30 Hz), from the prefrontal cortex or sensorimotor cortex. PCP (0.1-3 mg kg~(-1) s.c.) caused a marked dose-dependent increase in EEG power in the frontal cortex at 1-3 Hz with decreases in power at higher frequencies (9-30 Hz). At high doses (3 mg kg~(-1) s.c.) the entire spectrum shifted to more positive values, indicating an increase in cortical synchronization. MK 801 (0.05-0.1 mg kg~(-1) i.p.) caused similar effects but with lesser changes in power. 2 In contrast, the non-competitive AMPA antagonists GYKI 52466 and GYKI 53655 increased EEG power over the whole power spectrum (1-10 mg kg~(-1) i.p.). The atypical antipsychotic clozapine (0.2 mg kg~(-1) s.c.) synchronized the EEG (peak 8 Hz). The 5-HT_(2A)-antagonist, M100907, specifically increased EEG power at 2-3 Hz at low doses (10 and 50 μg kg~(-1) s.c.), whereas at higher doses (0.1 mg kg~(-1) s.c.) the profile resembled that of clozapine. 3 Clozapine (0.2 mg kg~(-1) s.c.), GYKI 53655 (5 mg kg~(-1) i.p.), prazosin (0.05 and 0.1 mg kg~(-1) i.p.), and M100907 (0.01 and 0.05 mg kg~(-1) s.c.) antagonized the decrease in power between 5 and 30 Hz caused by PCP (1 mg kg~(-1) s.c.), but not the increase in power at 1-3 Hz in prefrontal cortex.