Nicotine-induced sensitization in mice: changes in locomotor activity and mesencephalic gene expression
| Autor: | Csaba Vadasz, Ray Wang, Mariko Saito, Krisztina M. Kovacs, Danielle O’Brien, Jiri Zavadil |
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| Rok vydání: | 2005 |
| Předmět: |
Nicotine
Microarray Phosphatase Molecular Sequence Data Biology Pharmacology Motor Activity Biochemistry Midbrain Cellular and Molecular Neuroscience Mice Mesencephalon Gene expression medicine Animals Receptor Sensitization Mice Inbred BALB C Base Sequence Behavior Animal Dopaminergic General Medicine Mice Inbred C57BL medicine.anatomical_structure Gene Expression Regulation Female medicine.drug |
| Zdroj: | Neurochemical research. 30(8) |
| ISSN: | 0364-3190 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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