Addiction Rehab: Involvement of Protein Degradation by the Ubiquitin Proteasome System in Opiate Addictive Behaviors.
Involvement of Protein Degradation by the Ubiquitin Proteasome System in Opiate Addictive Behaviors.
Filed under: Addiction Rehab
Neuropsychopharmacology. 2012 Nov 21;
Massaly N, Dahan L, Baudonnat M, Hovnanian C, Rekik K, Solinas M, David V, Pech S, Zajac JM, Roullet P, Mouledous L, Frances B
Plastic changes in the nucleus accumbens (NAcc), a structure occupying a key position in the neural circuitry related to motivation, are among the critical cellular processes responsible for drug addiction. During the last decade, it has been shown that memory formation and related neuronal plasticity may rely not only on protein synthesis but also on protein degradation by the ubiquitin proteasome system (UPS). In this study, we assess the role of protein degradation in the NAcc in opiate-related behaviors. For this purpose, we coupled behavioral experiments to intra-accumbens injections of lactacystin, an inhibitor of the UPS. We show that protein degradation in the NAcc is mandatory for a full range of animal models of opiate addiction including morphine locomotor sensitization, morphine conditioned place preference, intra-ventral tegmental area morphine self-administration and intra-venous heroin self-administration but not for discrimination learning rewarded by highly palatable food. This study provides the first evidence of a specific role of protein degradation by the UPS in addiction.Neuropsychopharmacology advance online publication, 21 November 2012; doi:10.1038/npp.2012.217.
HubMed – addiction
The Synaptic Adhesion Molecule SynCAM 1 Contributes to Cocaine Effects on Synapse Structure and Psychostimulant Behavior.
Filed under: Addiction Rehab
Neuropsychopharmacology. 2012 Nov 21;
Giza JI, Jung Y, Jeffrey RA, Neugebauer NM, Picciotto MR, Biederer T
Drugs of abuse have acute and persistent effects on synapse structure and addiction-related behaviors. Trans-synaptic interactions can control synapse development, and synaptic cell adhesion molecule (SynCAM) proteins (also named nectin-like molecules) are immunoglobulin adhesion proteins that span the synaptic cleft and induce excitatory synapses. Our studies now reveal that the loss of SynCAM 1 in knockout (KO) mice reduces excitatory synapse number in nucleus accumbens (NAc). SynCAM 1 additionally contributes to the structural remodeling of NAc synapses in response to the psychostimulant cocaine. Specifically, we find that cocaine administration increases the density of stubby spines on medium spiny neurons in NAc, and that maintaining this increase requires SynCAM 1. Furthermore, mushroom-type spines on these neurons are structurally more plastic when SynCAM 1 is absent, and challenging drug-withdrawn mice with cocaine shortens these spines in SynCAM 1 KO mice. These effects are correlated with changes on the behavioral level, where SynCAM 1 contributes to the psychostimulant effects of cocaine as measured after acute and repeated administration, and in drug-withdrawn mice. Together, our results provide evidence that the loss of a synapse-organizing adhesion molecule can modulate cocaine effects on spine structures in NAc and increases vulnerability to the behavioral actions of cocaine. SynCAM-dependent pathways may therefore represent novel points of therapeutic intervention after exposure to drugs of abuse.Neuropsychopharmacology advance online publication, 21 November 2012; doi:10.1038/npp.2012.226.
HubMed – addiction
Functional genomic screening to enhance oncolytic virotherapy.
Filed under: Addiction Rehab
Br J Cancer. 2012 Nov 20;
Mahoney DJ, Stojdl DF
Functional genomic screening has emerged as a powerful approach for understanding complex biological phenomena. Of the available tools, genome-wide RNA interference (RNAi) technology is unquestionably the most incisive, as it directly probes gene function. Recent applications of RNAi screening have been impressive. Notable amongst these are its use in elucidated mechanism(s) for signal transduction, various aspects of cell biology, tumourigenesis and metastasis, resistance to cancer therapeutics, and the host’s response to a pathogen. Herein we discuss how recent RNAi screening efforts have helped turn our attention to the targetability of non-oncogene support pathways for cancer treatment, with a particular focus on a recent study that identified a non-oncogene addiction to the ER stress response as a synergist target for oncolytic virus therapy (OVT). Moreover, we give our thoughts on the future of RNAi screening as a tool to enhance OVT and describe recent technical improvements that are poised to make genome-scale RNAi experiments more sensitive, less noisy, more applicable in vivo, and more easily validated in clinically relevant animal models.British Journal of Cancer advance online publication, 20 November 2012; doi:10.1038/bjc.2012.467www.bjcancer.com.
HubMed – addiction
Internet addiction rehab helps students kick the habit – SUBSCRIBE to Next Media Animation: www.youtube.com Internet addiction has become a serious issue among young students in Taiwan, at least that’s what Taiwanese politicians are saying. To prevent “deviant behavior” and other social issues resulted to internet addiction among students, the government has introduced internet addiction rehab for kids. Carol’s Facebook: www.facebook.com Facebook: www.facebook.com Webpage: www.nma.tv Twitter @nmatv: twitter.com Tumblr: nmatv.tumblr.com According to a study from National Changhua University of Education, 20 percent of Taiwanese students are internet addicts, just slightly behind South Korea, which has the worst internet addiction rate for children in Asia. Withdraw symptoms can occur if addicts are prevented from going online. Psychotherapy and medical treatment may be required to assist the process of rehabilitation.
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