Nicotine-Induced Sensitization in Mice: Changes in Locomotor Activity and Mesencephalic Gene Expression |
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Authors: | Email author" target="_blank">Mariko?SaitoEmail author Danielle?O’Brien Krisztina?M?Kovacs Ray?Wang Jiri?Zavadil Csaba?Vadasz |
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Institution: | (1) Laboratory of Neurobehavioral Genetics, Nathan S. Kline Institute for Psychiatric Research, 140 Old Orangeburg Road, Orangeburg, NY 10962, USA;(2) Department of Psychiatry, New York University School of Medicine, New York, NY 10016, USA;(3) Department of Pathology, New York University School of Medicine, New York, NY 10016, USA;(4) Genomics Facility, New York University Cancer Institute, New York, NY 10016, USA |
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Abstract: | It is believed that drug-induced behavioral sensitization is an important process in the development of substance dependence.
In order to explore mechanisms of sensitization, a mouse model of nicotine-induced locomotor sensitization was established,
and effects of the sensitization process on mesencepahlic gene expression were examined. A schedule, which included 3 weeks
of intermittent nicotine exposure (0.5 mg/kg, s.c.) and 3 weeks of withdrawal, resulted in locomotor sensitization. Effects
of sensitization on mesencephalic expression of approximately 14,000 genes were assessed using oligonucleotide microarrays.
Signal intensity differences in samples obtained from repeated nicotine- and saline-exposed animals were analyzed with z-test
after False Discovery Rate (FDR) multiple test correction. Genes related to GABA-A receptors and protein phosphatases were
among 68 genes showing significantly different expression levels between the saline and the nicotine groups. We hypothesize
that some of the gene expression changes in the mesencephalon are involved in pathways leading to nicotine-induced sensitization.
Down-regulation of GABA-A receptors induced by repeated nicotine exposure may facilitate dopaminergic neuronal transmission
and may contribute to increased locomotor activity. |
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Keywords: | GABA-A receptors locomotor sensitization microarray mouse nicotine |
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