Changes in EEG spectral power in the prefrontal cortex of conscious rats elicited by drugs interacting with dopaminergic and noradrenergic transmission.

1. The electroencephalographic (EEG) effects of drugs interacting with dopaminergic and noradrenergic systems were studied in conscious rats. Power spectra (0 - 30 Hz) were recorded from electrodes implanted bilaterally in the prefrontal cortex. Drug effects on EEG power were calculated as the spectral power following drug administration divided by the spectral power after vehicle administration. 2. Dopaminergic agonists at low doses, (apomorphine 0. 01 mg kg-1 s.c., quinpirole 0.01 mg kg-1 i.p.) and dopaminergic antagonists (haloperidol 1 mg kg-1 i.p., raclopride 2.5 mg kg-1 s.c. ), which decrease dopaminergic transmission, induced an increase of EEG power. Conversely, dopaminergic agonists at higher doses (apomorphine 0.5 mg kg-1 s.c., quinpirole 0.5 mg kg-1 i.p.) which increase activation of postsynaptic D2 and D3 receptors, induced a decrease of EEG power. 3. The alpha1-adrenoceptor antagonists (phenoxybenzamine 0.64 mg kg-1 s.c., prazosin 0.32 mg kg-1 s.c.) and the alpha2-adrenoceptor agonists (UK 14304 0.05 mg kg-1 s.c., clonidine 0.025 mg kg-1 i.p.), which decrease noradrenergic transmission, induced an increase of EEG power. Conversely, the alpha1-adrenoceptor agonist, cirazoline (0.05 mg kg-1 s.c.), the adrenergic agent modafinil (250, 350 mg kg-1 i.p.) and alpha2-adrenoceptor antagonists (RX 821002 0.01 mg kg-1 s.c., yohimbine 0.5 mg kg-1 i.p.), which increase noradrenergic transmission, induced a decrease of EEG power. The effects of prazosin (0.64 mg kg-1 s.c.) were dose-dependently antagonized by co-administration with modafinil and cirazoline, but not by apomorphine. 4. In conclusion, pharmacological modulation of dopaminergic and noradrenergic transmission may result in consistent EEG changes: decreased dopaminergic or noradrenergic activity induces an increase of EEG spectral power; while increased dopaminergic or noradrenergic activity decreases EEG spectral power.

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.