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Methamphetamine (METH) preconditioning causes subsensitivity to METH‐induced acute effects on the expression of immediate early genes
Author(s) -
McCoy Michael Thomas,
Jayanthi Subramaniam,
Beauvais Genevieve,
Ladenheim Bruce,
Krasnova Irina,
Martin Tracey,
Hodges Amber B,
Cadet Jean Lud
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.507.4
Acute administration of Methamphetamine (METH) in animals causes substantial changes in the levels of transcripts that code for several immediate early genes. In the present study, we assessed the effects of chronic METH exposure on the acute effects of the drug. Towards that end, we administered either saline injections or increasing doses of METH over a two‐week period. After a one day withdrawal, the animals were injected with a dose of METH (5 mg/kg). Animals were euthanized at 2 hours after the drug injection. Their brains were rapidly removed and processed for measurements of mRNA levels by qRT‐PCR. The single METH injection caused increases in the gene expression of c‐fos, fosB, fra2, junB, junD, Egr1, Egr2, and Egr3. Chronic METH preconditioning alone caused reduction in the expression of c‐fos, fosB, fra1, junB, Egr1, Egr2, and Egr3. Moreover, chronic METH exposure caused substantial blunting of the acute effects of METH on the gene expression. Thus, that repeated injections of METH can cause substantial changes in the expression of genes that regulate in a number of cellular functions in the brain. The possibility that these METH preconditioning‐induced alterations are due to METH‐induced epigenetic changes in the striatum is being investigated. This work is supported Department of Health and Human Services/National Institutes of Health/National Institute on Drug Abuse/Intramural Research Program.