Effects of dopamine antagonists on changes in spontaneous EEG and locomotor activity in ketamine-treated rats.
We investigated the effects of dopamine antagonists on spontaneous cortical and hippocampal electroencephalographic (EEG) changes, and on hyperlocomotion in ketamine-treated rats. Ketamine (20-60 mg/kg IP) synchronized cortical EEG and desynchronized hippocampal EEG in a dose-dependent manner indicating that the drug induced a dissociation between the cortical and hippocampal EEG. These EEG changes were accompanied by an increase in spontaneous locomotor activity, which involved lack of focused direction, stereotypy, irritability and other abnormalities. Dopamine antagonists, such as haloperidol (0.3-1 mg/kg IP), and nemonapride (0.3-1 mg/kg IP), reversed the dissociation between the cortical and hippocampal EEG in ketamine (60 mg/kg IP)-treated rats. Ketamine-induced hyperlocomotion was also decreased by administration of haloperidol (0.3 and 1 mg/kg IP) or nemonapride (0.1-1 mg/kg IP). Thus, it was found that dopamine antagonists reversed the EEG alterations and behavioural changes in ketamine-treated rats.
Yamamoto
M
M
Clinical Pharmacology Res. Lab., Yamanouchi Pharmaceutical Co. Ltd., Tokyo, Japan.
Mizuki
Y
Y
Suetsugi
M
M
Ozawa
Y
Y
Ooyama
M
M
Suzuki
M
M
D000704:Analysis of Variance; D000818:Animals; D001549:Benzamides / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000187:drug effects; D018492:Dopamine Antagonists / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D004569:Electroencephalography / Q000187:drug effects*; D006220:Haloperidol / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects; D007649:Ketamine / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar
D001549:Benzamides; D018492:Dopamine Antagonists; D007649:Ketamine; D006220:Haloperidol; C030265:nemonapride