Adaptation to repeated cocaine administration in rats.
Quantitative electroencephalogram (EEG) studies in cocaine-dependent human patients show deficits in slow-wave brain activity, reflected in diminished EEG power in the delta and theta frequency bands. In the present study, electrophysiological measures were monitored in 10 nonanesthetized, adult male Sprague-Dawley rats via bipolar, epidural electrodes implanted over the somatosensory cortex. Control electrocorticograms (ECoG) were recorded twice within a two-week interval to establish a baseline. Rats were subsequently injected daily with cocaine HCl at 15 mg/kg, i.p., for two weeks. The ECoG was recorded during a 1-h session one day after the last injection. Total concentrations of dopamine (DA) and its metabolites were assayed in caudate nucleus (CN) and frontal cortex (FC) using HPLC/EC. Compared with controls, marked increases in DA concentrations were observed in both regions. The DA turnover decreased significantly. The power spectra, obtained by use of a fast Fourier transformation, revealed a significant decrease in slow-wave delta frequency bands following repeated exposure to cocaine. These data are consistent with reported findings in humans that repeated exposures to cocaine result in a decrease in slow-wave brain activity. Further studies are necessary to establish whether regional alterations in blood flow and metabolic activity may underlie such observations.
Binienda
Zbigniew K
ZK
Division of Neurotoxicology, NCTR/FDA, Jefferson, Arkansas 72029, USA. zbinienda@nctr.fda.gov
Pereira
Frederico
F
Alper
Kenneth
K
Slikker
William
W
Ali
Syed F
SF
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D002421:Caudate Nucleus / Q000187:drug effects / Q000378:metabolism; D003042:Cocaine / Q000008:administration & dosage*; D019970:Cocaine-Related Disorders / Q000503:physiopathology* / Q000523:psychology; D003344:Cortical Synchronization / Q000187:drug effects; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D004334:Drug Administration Schedule; D004569:Electroencephalography / Q000187:drug effects; D005625:Frontal Lobe / Q000187:drug effects / Q000378:metabolism; D006719:Homovanillic Acid / Q000378:metabolism; D006801:Humans; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D015102:3,4-Dihydroxyphenylacetic Acid; D003042:Cocaine; D004298:Dopamine; D006719:Homovanillic Acid