Relationship between electrocortical activity and beta-adrenergic receptor function in the rat after chronic desimipramine treatment.
The aim of this study was to investigate the effects of chronic administration of desimipramine (DMI) after 2, 7 or 20 mg/kg per day, administered by osmotic minipumps, on electrocortical activity and beta-adrenergic receptors in rat brain. Rats receiving DMI chronically show a dose- and time-dependent increase of electrocortical activity above 15 Hz as well as a dose- and time-dependent decrease below 15 Hz. Already after 3 days of treatment a clear effect on the electrocorticogram (ECoG) was seen. The maximal change in the ECoG was reached at the end of the study, after 24 days of treatment. After acute treatment (20 and 45 minutes after 2, 4 or 10 mg/kg i.p.) with DMI, a decrease of electrocortical activity is seen above 15 Hz. Thus the effect of acute DMI treatment on the ECoG is different from that of chronic treatment. In the same group of rats the effect of chronic DMI treatment on the beta-adrenergic receptor number was determined 24 hours after the last ECoG recording. The number of beta-adrenergic receptors was dose dependently reduced in the DMI-treated rats as determined by [3H]-dihydroalprenolol binding. There was no change in affinity (KD) of the ligand for the beta-receptor. This finding was corroborated by a decrease in the functional activity of the beta-adrenergic receptors, as determined by isoprenaline stimulated efflux of cyclic-AMP in cortex slices. These data indicate that chronic treatment with DMI, resulting in a down-regulation of the cortical beta-adrenergic system, is paralleled by pronounced effects on the ECoG of rats. The different ECoG profiles after chronic DMI treatment compared with acute treatment suggest that adaptive changes in the electrical brain activity continually develop during the chronic treatment with this antidepressant drug.
Krijzer
F N
FN
Department of Pharmacology, Duphar B.V., Weesp, The Netherlands.
Schipper
J
J
Tulp
M T
MT
Koopman
P A
PA
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000502:physiology; D003891:Desipramine / Q000494:pharmacology*; D004569:Electroencephalography; D004594:Electrophysiology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000187:drug effects* / Q000502:physiology
D011943:Receptors, Adrenergic, beta; D003891:Desipramine