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

1 Power spectra (0-30 Hz) were recorded from transcortical electrodes impla nted in prefrontal and sensorimotor cortex in conscious rats. For each anim al. the spectra in the presence of a drug were divided by the spectra in th e presence of vehicle to give a drug-related differential display of the po wer spectra, the profile of EFG effects. 2 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 (1.5 mg kg(-1), s.c., peak 9-12 Hz), serti ndole (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, incre asing the power spectra between 2 and 30 Hz, although there were marked dif ferences between the individual profile of EEG effects for each drug. 3 In contrast, the benzamides, sulpiride (7.5 and 15 mg kg(-1) i.p.), and a misulpiride (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. 4 Modafinil and apomorphine, administered alone, decreased the power spectr a at frequencies higher than 4 Hz. Modafinil (62.4 mg kg(-1), i.p.) selecti vely antagonized the effects of clozapine, but did not antagonize the effec ts of raclopride. 5 Different pharmacological classes of antipsychotic show synchronization o r desynchronization of the EEG in the prefrontal cortex, with the benzamide s showing a distinctive spectrum. There appears to be a specific interactio n between modafinil and clozapine. Thus, modulation of prefrontal cortical function, perhaps by thalamic gating, may be important for antipsychotic ac tivity.