Contrasting EEG profiles elicited by antipsychotic agents in the prefrontal cortex of the conscious rat: antagonism of the effects of clozapine by modafinil


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  • Power spectra (0–30 Hz) were recorded from transcortical electrodes implanted in prefrontal and sensorimotor cortex in conscious rats. For each animal, the spectra in the presence of a drug were divided by the spectra in the presence of vehicle to give a drug-related differential display of the power spectra, the profile of EEG effects.

  • The profiles of a range of antipsychotic agents of different classes were compared. Haloperidol (0.5 mg kg−1 and 1 mg kg−1 s.c., peak 8–12 Hz), chlorpromazine (0.5 mg kg−1, i.p., peak 8 Hz), levomepromazine (1 mg kg−1, i.p., peak 8 Hz), quetiapine (2.5 mg kg−1, s.c., peak 9–12 Hz), sertindole (2.5 mg kg−1, s.c., peak 6–14 Hz), risperidone (0.5 and 1 mg kg−1 i.p., peak 9 Hz), clozapine (0.1, 0.2, 0.3 and 5 mg kg−1, s.c., peak 8 Hz) and MDL100907 (0.01 mg kg−1 s.c. peak 2 Hz) synchronized the EEG, increasing the power spectra between 2 and 30 Hz, although there were marked differences between the individual profile of EEG effects for each drug.

  • In contrast, the benzamides, sulpiride (7.5 and 15 mg kg−1 i.p.), and amisulpiride (1 and 15 mg kg−1 i.p.) caused marked asynchronous changes in the EEG. Raclopride (2.5 mg kg−1 i.p.), caused an initial peak at 9 Hz, but the effects of raclopride desynchronized over a 3 h time period.

  • Modafinil and apomorphine, administered alone, decreased the power spectra at frequencies higher than 4 Hz. Modafinil (62.4 mg kg−1, i.p.) selectively antagonized the effects of clozapine, but did not antagonize the effects of raclopride.

  • Different pharmacological classes of antipsychotic show synchronization or desynchronization of the EEG in the prefrontal cortex, with the benzamides showing a distinctive spectrum. There appears to be a specific interaction between modafinil and clozapine. Thus, modulation of prefrontal cortical function, perhaps by thalamic gating, may be important for antipsychotic activity.

British Journal of Pharmacology (1999) 128, 1055–1063; doi:10.1038/sj.bjp.0702893