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Cocaine Treatment (cocaine + treatment)
Selected AbstractsTime course of striatal ,FosB-like immunoreactivity and prodynorphin mRNA levels after discontinuation of chronic dopaminomimetic treatmentEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 3 2003M. Andersson Abstract ,FosB-like proteins are particularly stable transcription factors that accumulate in the brain in response to chronic perturbations. In this study we have compared the time-course of striatal FosB/,FosB-like immunoreactivity and prodynorphin mRNA expression after discontinuation of chronic cocaine treatment to intact rats and chronic L-DOPA treatment to unilaterally 6-hydroxydopamine (6-OHDA) lesioned rats. The animals were killed between 3 h and 16 days after the last drug injection. In both treatment paradigms, the drug-induced FosB/,FosB immunoreactivity remained significantly elevated in the caudate putamen even at the longest withdrawal period examined. The concomitant upregulation of prodynorphin mRNA, a target of ,FosB, paralleled the time-course of ,FosB-like immunoreactivity in the 6-OHDA-lesion/L-DOPA model, but was more transient in animals treated with cocaine. These results suggest that ,FosB-like proteins have exceptional in vivo stability. In the dopamine-denervated striatum, these proteins may exert sustained effects on the expression of their target genes long after discontinuation of L-DOPA pharmacotherapy. [source] Matrix-assisted laser desorption/ionization tissue profiling of secretoneurin in the nucleus accumbens shell from cocaine-sensitized ratsJOURNAL OF MASS SPECTROMETRY (INCORP BIOLOGICAL MASS SPECTROMETRY), Issue 1 2010Joachim D. Uys Abstract Proteins in the nucleus accumbens mediate many cocaine-induced behaviors. In an effort to measure changes in nucleus accumbens protein expression as potential biomarkers for addiction, coronal tissue sections were obtained from rats that developed behavioral sensitization after daily administration of cocaine, or from daily saline-treated controls. The tissue sections were subjected to matrix-assisted laser desorption/ionization (MALDI) mass spectrometry (MS) profiling and tissue imaging. For profiling experiments, brain sections were manually spotted with matrix over the nucleus accumbens, a brain region known to regulate cocaine sensitization. Summed mass spectra (10 000 laser shots, grid) were acquired and spectra were aligned to reference peaks. Using bioinformatics tools, eight spectral features were found to be altered by cocaine treatment. Based on additional sequencing experiments with MALDI tandem MS and database searches of measured masses, secretoneurin (m/z 3653) was identified as having an increased expression. In addition, the distribution of m/z 3653 in the nucleus accumbens was determined by MALDI tissue imaging, and the increased expression of its precursor protein, secretogranin II, was verified by immunoblotting. Copyright © 2009 John Wiley & Sons, Ltd. [source] Neural plasticity and addiction: integrin-linked kinase and cocaine behavioral sensitizationJOURNAL OF NEUROCHEMISTRY, Issue 3 2008Qiang Chen Abstract Behavioral sensitization of psychostimulants was accompanied by alterations in a variety of biochemical molecules in different brain regions. However, which change is actually related to drug-produced sensitization lacks of accurate clarification. In this study, we investigated the role of integrin-linked kinase (ILK) in both the induction and expression of cocaine sensitization. Conditional inhibition of ILK expression was established in the nucleus accumbens (NAc) core by microinjecting recombinant adeno-associated virus-carrying, tetracycline-on-regulated small interfering RNA which reversed the chronic cocaine-induced psychomotor sensitization, as well as the changes in protein kinase B Ser473 phosphorylation, dendritic density, and dendritic spine numbers locally. Importantly, the reversed psychomotor sensitization did not recover after cessation of the silencing for 8 days. We also demonstrated that inhibition of ILK expression pre- and during-chronic cocaine treatments blocked the induction of cocaine psychomotor sensitization and abolished the stimulant effect of cocaine on ILK expression. In contrast, inhibition of ILK expression in the NAc core has no significant effect on cocaine-induced stereotypical behaviors. This concludes that ILK is involved in cocaine sensitization with the earlier induction and later expression functioning as a kinase to regulate protein kinase B Ser473 phosphorylation and a scaffolding protein to regulate the reorganization of the NAc spine morphology. [source] Long-lasting up-regulation of orexin receptor type 2 protein levels in the rat nucleus accumbens after chronic cocaine administrationJOURNAL OF NEUROCHEMISTRY, Issue 1 2007Guo-Chi Zhang Abstract Hypothalamic orexin (hypocretin) neurons project to the key structures of the limbic system and orexin receptors, both orexin receptor type 1 (OXR1) and type 2 (OXR2), are expressed in most limbic regions. Emerging evidence suggests that orexin is among important neurotransmitters that regulate addictive properties of drugs of abuse. In this study, we examined the effect of psychostimulant cocaine on orexin receptor protein abundance in the rat limbic system in vivo. Intermittent administration of cocaine (20 mg/kg, i.p., once daily for 5 days) caused a typical behavioral sensitization response to a challenge cocaine injection at a 14-day withdrawal period. Repeated cocaine administration at the same withdrawal time also increased OXR2 protein levels in the nucleus accumbens while repeated cocaine had no effect on OXR1 and orexin neuropeptide (both orexin-A and orexin-B) levels in this region. In contrast to the nucleus accumbens, OXR2 levels in the frontal cortex, the ventral tegmental area, the hippocampus, and the dorsal striatum (caudate putamen) were not altered by cocaine. Remarkably, the up-regulated OXR2 levels in the nucleus accumbens showed a long-lasting nature as it persisted up to 60 days after the discontinuation of repeated cocaine treatments. In contrast to chronic cocaine administration, an acute cocaine injection was insufficient to modify levels of any orexin receptor and peptide. Our data identify the up-regulation of OXR2 in the nucleus accumbens as an enduring molecular event that is correlated well with behavioral plasticity in response to chronic psychostimulant administration. This OXR2 up-regulation may reflect a key adaptation of limbic orexinergic transmission to chronic drug exposure and may thus be critical for the expression of motor plasticity. [source] | ||||||||||