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 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. 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 (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. 3. 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. 4 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. 5. 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.
Sebban
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Laboratoire de Biologie du Vieillissement, Hopital Charles Foix, 7 avenue de la République, 94205 Ivry sur Seine cedex, France.
Tesolin-Decros
B
B
Millan
M J
MJ
Spedding
M
M
D000818:Animals; D014150:Antipsychotic Agents / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D001058:Apomorphine / Q000494:pharmacology; D001559:Benzhydryl Compounds / Q000494:pharmacology*; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D003024:Clozapine / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D018491:Dopamine Agonists / Q000494:pharmacology; D004569:Electroencephalography / Q000187:drug effects*; D007279:Injections, Subcutaneous; D008297:Male; D000077408:Modafinil; D009044:Motor Cortex / Q000187:drug effects; D017397:Prefrontal Cortex / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D013003:Somatosensory Cortex / Q000187:drug effects
D014150:Antipsychotic Agents; D001559:Benzhydryl Compounds; D000697:Central Nervous System Stimulants; D018491:Dopamine Agonists; D003024:Clozapine; D001058:Apomorphine; D000077408:Modafinil