Chronic Nicotine Doses Down-Regulate PDE4 Isoforms that Are Targets of Antidepressants in Adolescent Female Rats
| Autor: | Oksana Polesskaya, Karl J. Fryxell, Robert F. Smith |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Nicotine
medicine.medical_specialty medicine.medical_treatment Down-Regulation Hippocampus Pharmacology Nucleus accumbens Drug Administration Schedule PDE4B Internal medicine medicine Animals Humans Protein Isoforms Tissue Distribution Nicotinic Agonists RNA Messenger Prefrontal cortex Biological Psychiatry Rolipram Oligonucleotide Array Sequence Analysis Analysis of Variance Depression Reverse Transcriptase Polymerase Chain Reaction business.industry Brain Chromosome Mapping Cyclic Nucleotide Phosphodiesterases Type 4 Rats Disease Models Animal Endocrinology Animals Newborn 3' 5'-Cyclic-AMP Phosphodiesterases Antidepressant Smoking cessation Female business medicine.drug |
| Zdroj: | Biological Psychiatry. 61:56-64 |
| ISSN: | 0006-3223 |
| Popis: | Background Previous data in humans and animal models has suggested connections between anxiety, depression, smoking behavior, and nicotine dependence. The importance of these connections has been confirmed by clinical studies that led to the recent FDA approval of an anti-depressant (Zyban) for use in human smoking cessation programs. Other anti-depressants (such as rolipram) specifically inhibit PDE4 phosphodiesterases. Methods We used DNA microarrays to discover gene expression changes in adolescent female rats following chronic nicotine treatments, and real-time PCR assays to confirm and extend those results. Results We found a consistent decrease in the mRNA levels encoded by the Pde4b gene in nucleus accumbens, prefrontal cortex, and hippocampus of adolescent female rats treated with .24 mg/day nicotine, and in prefrontal cortex of adolescent female rats treated with .12 mg/day nicotine. We further show that each of these brain areas produced a different profile of Pde4b isoforms. Conclusions Chronic nicotine treatments produce a dose-dependent down-regulation of Pde4b, which may have an antidepressant effect. This is the first report of a link between nicotine dependence and phosphodiesterase gene expression. Our results also add to the complex interrelationships between smoking and schizophrenia, because mutations in the PDE4B gene are associated with schizophrenia. |
| Databáze: | OpenAIRE |
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