Original articleChronic Nicotine Doses Down-Regulate PDE4 Isoforms that Are Targets of Antidepressants in Adolescent Female Rats
Section snippets
Animals, Dosing Protocol, and Tissue Preparation
All animal protocols were reviewed and approved by IACUC of George Mason University. Nicotine bitartrate in .9% sodium chloride was chronically administered from postnatal day 22 (p22) to p36 via an osmotic pump (Alzet, Durect Co, Cupertino, California), and replaced with a second osmotic pump delivering the same dose from p36 to p45 as previously described (McDonald et al 2005). Osmotic pumps deliver reproducible doses without some of the potential complications that accompany nicotine
Preliminary DNA Microarray Experiments Implicated Pde4b as Being Down-Regulated by Nicotine in Several Brain Areas
Preliminary DNA microarray experiments utilized two treatments: the “high dose” females received .24 mg of nicotine per day, resulting in plasma nicotine concentrations equivalent to those of human heavy smokers (see Methods and Materials). The “normal” group were untreated female littermates of the same age. For RT-PCR experiments, female littermates implanted with saline-filled osmotic pumps were used as controls (see below). Three brain areas were studied: NA, PFC, and H.
DNA microarray data
Discussion
The first cyclic nucleotide phosphodiesterase gene to be identified was the Drosophila dunce gene, so named because it plays a key role in complex behaviors such as learning (Chen et al 1986, Dudai et al 1976, Shotwell 1983). There are four human genes that are closely related to dunce (the PDE4 gene family), and these account for the majority of the cyclic AMP hydrolyzing activity in most mammalian cells (Conti et al 2003). Each of the genes in the mammalian PDE4 gene family (PDE4A, PDE4B,
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2007, Current Opinion in NeurobiologyCitation Excerpt :Other variants of PDE4B are also associated with schizophrenia [51]. Chronic nicotine exposure downregulates Pde4b mRNA levels in the hippocampus, prefrontal cortex and nucleus accumbens of female rats [52] (Figure 2). As Polesskaya et al. [52] point out, this is an interesting observation because tobacco use is highly prevalent among individuals with schizophrenia and depression, perhaps owing to ‘self-medication’.
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2007, Annual Reports in Medicinal ChemistryCitation Excerpt :Furthermore, use of PDE4D knockout mice showed that the anti-psychotic effects of rolipram are mediated to a large extent through PDE4B [26]. Of interest to schizophrenia is a recent publication showing that chronic nicotine administration downregulates expression of PDE4 isoforms in rats [27]. The high rate of smoking in schizophrenic patients may be a form of self-medication in which nicotine intake decreases PDE4 enzyme activity by regulating its expression.
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2007, Neurotoxicology and TeratologyCitation Excerpt :Tissue samples were rapidly frozen and stored at − 80 °C. RNA was purified from frozen tissue samples as previously described [74]. Five μg of total RNA were used for amplification (MessageAmp aRNA kit, Ambion) according to manufacturer's instructions.
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