Biochemical and Biophysical Research Communications
PI3 kinase is involved in cocaine behavioral sensitization and its reversal with brain area specificity☆,☆☆
Section snippets
Materials and methods
Animals and drugs. Male Sprague–Dawley rats, initially weighing 150–200 g (Charles River Laboratories), were acclimated for 1 week prior to the experiments. Rats were housed in pairs in plastic cages in a humidity- and temperature-controlled room on a 12-h light/dark cycle. All experiments were conducted with an approved protocol from the Duke University Institutional Animal Care and Use Committee and were performed in accordance with NIH guideline (NIH publication 865-23). Cocaine HCl (NIDA)
Pergolide/ondansetron reverses cocaine-induced locomotor activation
In our experimental design, animals were given saline or cocaine for 4 days followed by a 9-days withdrawal period to establish behavioral sensitization in the cocaine group. Both cocaine and saline groups were then given pergolide/ondansetron, pergolide/saline or vehicles (DMSO/saline), followed by another 9-days withdrawal before being challenged with acute cocaine for sensitization assessment. The locomotor stimulation by cocaine challenge was measured for 30 min (Fig. 1). One-way ANOVA
Discussion
Cocaine dependence is a common and serious public health problem. To date, no pharmacological treatment is available that can consistently lead to long-term cocaine abstinence [26], [27]. This general lack of effective pharmacotherapy is largely due to the fact that the molecular basis of continued cocaine vulnerability following long-term withdrawal has been only partially elucidated. In rats, repeated administration of cocaine leads to behavioral sensitization, and this behavioral alteration
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2013, PainCitation Excerpt :While injury did not alter the expression or phosphorylation state of PKCε within the LP1 fraction (Fig. 2A), the levels of phospho-PKCε and the ratio of phosphorylated vs total PKCε were significantly elevated within the nuclear fraction at the 2-week time point (Fig. 2B) [phospho-PKCε: F(3, 56) = 4.95, P = 0.004; PKCε ratio: F(3, 51) = 13.06, P < 0.0001]. Elevations in the PSD levels of PI3K and of phospho-(Tyr)p85α PI3K binding motif (an index of PI3K activation [74]) were observed at 1 week postinjury (Fig. 2A) [PI3K: F(3, 51) = 3.93, P = 0.01; p(Tyr)p85αPI3K binding motif: F(3, 48) = 3.11, P = 0.03]. In contrast to the LP1 fraction, no significant changes in PI3K expression or activity were observed within the P1 fraction (Fig. 2B).
Oxidative stress mediates radiation lung injury by inducing apoptosis
2012, International Journal of Radiation Oncology Biology PhysicsCitation Excerpt :The analysis was performed by 2 independent observers who were unaware of the identity of the slides. The snap-frozen right lung was homogenized in ice-cold homogenization buffer (1% sodium deoxycholate, 5 mM Tris-HCL [pH 7.4], 2 mM ethylenediaminetetraacetic acid, 10 μg/mL aprotinin, 0.5 mM phenylmethylsulfonyl fluoride, 1 μM pepstatin A, and 0.1 mg/mL benzamidine with or without phosphatase inhibitors), and Western blot performed as previously described (11). Western blots were performed using lung tissue collected from 14 mice per group (sham-irradiated and IR alone) or 6 mice per group (sham irradiated plus AEOL10150 or IR plus AEOL10150).
Infusion of BDNF into the nucleus accumbens of aged rats improves cognition and structural synaptic plasticity through PI3K-ILK-Akt signaling
2012, Behavioural Brain ResearchCitation Excerpt :The primary antibodies [anti-TrkA, anti-TrkB, anti-p75NTR, anti-phospho-Akt (Ser473), anti-phospho-Akt (Thr308), anti-Akt, phospho-(Tyr) PI3K p85α binding motif, 1:1000 dilutions] and peroxidase-labeled secondary antibody (1:2000 dilution) were purchased from Cell Signaling Inc. (Berverly, MA). The PI3 kinase activity was determined by the level of p85α phospho-tyrosine binding motif detected by Western blot [13]. The blot was developed with chemiluminescent substrate (Santa Cruz Biotechnology, Santa Cruz, CA).
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This work was supported by National Institute on Drug Abuse (DA-10327 and DA-14323 to EHE and NS-42124 to THL).
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Abbreviations: DA, dopamine; PI3K, phosphatidylinositol 3-kinase; PFC, prefrontal cortex; NAc, nuclear accumbens; 5-HT, serotonin; NE, norepinephrine.