Synchronization of the EEG and sedation induced by neuroleptics depend upon blockade of both D1 and D2 dopamine receptors.
Blockade of dopamine (DA) receptors by neuroleptics tends to produce sedation, as shown by increased sleeping time, reduction of the arousal response to sensory stimuli and slowing of the electrical (EEG) activity of the brain. The EEG and behavioural effects of the selective compounds, SCH 23390 and raclopride, which block either D1 or D2 receptor subtypes, respectively were evaluated. Groups of rabbits were prepared for the measurement of EEG activity (neocortex and hippocampus). The EEG was analyzed visually and by spectral power analysis. Gross behaviour was also observed. The D1 antagonist, SCH 23390, by itself (0.03-0.3 mg/kg i.v.) produced small changes in the EEG and no evidence of sedation. Periods of slow waves occurred sporadically. Computerized EEG analysis showed moderate increases of total power density. The D2 receptor blocker, raclopride, alone (1-3 mg/kg i.v.) produced changes of the activity of the EEG, mostly, short periods of slow waves and slight increases of total power. No sedation was noted. Although both selective antagonists were studied at larger doses than those minimally effective, they produced slight EEG and behavioural changes which were not comparable with the marked actions produced by classical neuroleptics, such as haloperidol. However, when raclopride (1 mg/kg) was given after treatment with SCH 23390 (0.03 mg/kg) there was a marked synchronized activity in the EEG, associated with a state of sedation and diminished responsiveness to sensory stimuli. The data indicate that EEG synchronization and sedation, classically associated with treatment with neuroleptics, do not depend upon the selective blockade of either D1 or D2 receptors but, instead, require concurrent blockade of both subtypes of receptor.
Bo
P
P
Institute of Neurology C. Mondino, University of Pavia, School of Medicine, Italy.
Ongini
E
E
Giorgetti
A
A
Savoldi
F
F
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001552:Benzazepines / Q000494:pharmacology; D004347:Drug Interactions; D004569:Electroencephalography; D006220:Haloperidol / Q000494:pharmacology; D006993:Hypnotics and Sedatives; D011817:Rabbits; D020891:Raclopride; D011954:Receptors, Dopamine / Q000187:drug effects*; D012457:Salicylamides / Q000494:pharmacology
D014150:Antipsychotic Agents; D001552:Benzazepines; D006993:Hypnotics and Sedatives; D011954:Receptors, Dopamine; D012457:Salicylamides; D020891:Raclopride; D006220:Haloperidol