Methamphetamine-induced gene expression profiles in the striatum of male rat pups exposed to the drug in utero.
Methamphetamine is a neurotoxic pychostimulant which affects monoaminergic and non-monoaminergic systems in the brain. Clinical studies in humans have found that exposure to methamphetamine in the developing embryo can cause significant behavioral and cognitive anomalies later in life. Exposure of animals to methamphetamine (METH) in utero can cause neurobehavioral effects that do not become apparent until young adulthood. In the present study, we sought to determine the effects of in utero METH exposure on the striata of perinatal rat pups using a recently developed 17 k cDNA microarray. We found that METH administration caused alterations in 913 genes according to strict criteria. These alterations include changes in genes that participate in signal transduction, heat shock responses and neuronal development. The majority of the changes in gene expression were more prominent at the 7-day time point. These observations suggest that in utero METH exposure might initiate molecular programs that significantly impact gene expression during the developmental period long after the last exposure to this drug. Thus, during development, METH exposure in utero might cause significant long-term changes in gene expression that might constitute, in part, some of the substrates for the behavioral and cognitive anomalies reported in the literature.
Noailles
Pierre Antoine H
PA
Molecular Neuropsychiatry Branch, NIDA/NIH, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA.
Becker
Kevin G
KG
Wood
William H
WH
Teichberg
Diane
D
Cadet
Jean Lud
JL
D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D016000:Cluster Analysis; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology*; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley
D000697:Central Nervous System Stimulants; D018076:DNA, Complementary; D008694:Methamphetamine