Long-lasting abolishment of noradrenaline induced stimulation of oxidative metabolism after chronic exposure of developing mouse astrocytes to cocaine.
Rate of 14CO2 production from [l-14C]glutamate was determined as a measurement of oxidative metabolism in developing primary cultures of astrocytes, obtained from the neonatal mouse brain and grown in the absence (control) or presence of cocaine. From the age of 3 days, the drug-exposed cultures were grown in a tissue culture medium containing either 1 or 3 microM cocaine. After 2 months of chronic exposure to cocaine the metabolic rate showed an increase of approximately 50%, but there was a long lag period (several weeks) before this response occurred. In contrast to a marked stimulation of CO2 production when noradrenaline was added to untreated cultures of the same age, there was no similar effect of noradrenaline on cultures treated with cocaine. After exposure to cocaine for 21 days (24-day-old cultures), both the enhanced CO2 production and the abolishment of the normal response to noradrenaline persisted during 'withdrawal' (cessation of drug exposure) throughout the total period investigated, i.e. to an age of 60 days (corresponding to a withdrawal period of 36 days). The correlation of these findings with in vivo data is discussed.
Department of Pharmacology, University of Saskatchewan, Saskatoon, Canada.
L
L
Peng
L
L
Hertz
D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D001479:Basal Ganglia / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002245:Carbon Dioxide / Q000032:analysis; D002478:Cells, Cultured; D003042:Cocaine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005971:Glutamates / Q000378:metabolism*; D018698:Glutamic Acid; D006624:Hippocampus / Q000378:metabolism; D007700:Kinetics; D008578:Meninges / Q000378:metabolism; D051379:Mice; D009638:Norepinephrine / Q000494:pharmacology*; D009830:Olfactory Bulb / Q000378:metabolism; D009928:Organ Specificity; D010101:Oxygen Consumption / Q000187:drug effects; D019966:Substance-Related Disorders / Q000378:metabolism; D013997:Time Factors
D005971:Glutamates; D002245:Carbon Dioxide; D018698:Glutamic Acid; D003042:Cocaine; D009638:Norepinephrine