Search for genetic markers and functional variants involved in the development of opiate and cocaine addiction and treatment

Yuferov, Vadim; Levran, Orna; Proudnikov, Dmitri; Nielsen, David A.; Kreek, Mary Jeanne

doi:10.1111/j.1749-6632.2009.05275.x

Cited by 85 publications

(79 citation statements)

References 295 publications

(320 reference statements)

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“…Although knowledge of genetic markers associated with opioid addiction and treatment are beginning to emerge (Yuferov et al, 2010), the implications of these for effects of different opioids in humans remains unknown.…”

Section: Introductionmentioning

confidence: 99%

Analysis of opioid efficacy, tolerance, addiction and dependence from cell culture to human

Morgan

Christie

2011

British J Pharmacology

225

166

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Opioid agonists are the most effective treatment for pain, but their use is limited by side effects, tolerance and fears of addiction and dependence. A major goal of opioid research is to develop agonists that have high analgesic efficacy and a low profile for side effects, tolerance, addiction and dependence. Unfortunately, there is a serious lack of experimental data comparing the degree to which different opioids produce these effects in humans. In contrast, a wide range of experimental techniques from heterologous expression systems to behaviour assessment in whole animals have been developed to study these problems. The objective of this review is to describe and evaluate these techniques as they are used to study opioid efficacy, tolerance, addiction and dependence. LINKED ARTICLESThis article is part of a themed issue on Translational Neuropharmacology. To view the other articles in this issue visit http://dx.doi.org/10. 1111/bph.2011.164.issue-4 Abbreviations CNS, central nervous system; CPP, conditioned place preference; DAMGO, D-Ala(2),N-Me-Phe(4),Gly(5)-ol]-enkephalin; ERK1/2, extracellular signal regulated kinases 1 & 2; GIRK, G-protein coupled inward rectifying potassium channel; GTPgS, guanosine 5′-3′thio-triphosphate; HEK 293, human embryonic kidney 293 cells; Kv, voltage gated potassium channel IntroductionOpioids are the most effective treatment for pain. Unfortunately, opioid use is limited by serious adverse effects such as respiratory depression, sedation and constipation. The development of tolerance, dependence and addiction during chronic opioid use further limit the clinical utility of these drugs. Opioid tolerance is characterized by a reduced responsiveness to an opioid agonist such as morphine and is usually manifest by the need to use increasing doses to achieve the desired effect. Clinically, more than 10-fold dose escalations of opioid dose in chronic pain management are common (Buntin-Mushock et al., 2005) and yet, many studies show that relatively stable doses of opioids can provide pain relief for weeks or years (Eisenberg et al., 2005;Farrar et al., 2010). Addiction as defined by the compulsive, harmful use criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition is common among recreational opioid users, but relatively rare in chronic pain patients (Cowan et al., 2001). Conservative estimates of patients prescribed longterm opioids who develop some sort of addictive disorder range from 2-6% (Fields, 2007) although both lower and higher rates have been reported (Ballantyne and LaForge, 2007;Noble et al., 2010). The terms dependence and addiction are commonly used interchangeably, but the former will be used here in the context of the withdrawal syndrome that is characteristically observed on cessation of chronic opioid use or administration of opioid antagonists and the latter to models of compulsive drug use in animals and humans. Although animal studies have reported differences in analgesic efficacy, tolerance, addiction or withdrawal for diffe...

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Section: Introductionmentioning

confidence: 99%

Analysis of opioid efficacy, tolerance, addiction and dependence from cell culture to human

Morgan

Christie

2011

British J Pharmacology

225

166

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“…Polymorphisms in several genes, including genes encoding opioid receptors and ligands, were indicated in association with drug addiction (82)(83)(84). Here, we specifically discuss studies of the MOP-r gene (OPRM1), heroin addiction, and methadone maintenance treatment (MMT) for opioid addiction.…”

Section: The Genetics Of Drug Addictionsmentioning

confidence: 99%

Opiate addiction and cocaine addiction: underlying molecular neurobiology and genetics

Kreek¹,

Levran²,

Reed³

et al. 2012

J. Clin. Invest.

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189

121

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Addictive diseases, including addiction to heroin, prescription opioids, or cocaine, pose massive personal and public health costs. Addictions are chronic relapsing diseases of the brain caused by drug-induced direct effects and persisting neuroadaptations at the epigenetic, mRNA, neuropeptide, neurotransmitter, or protein levels. These neuroadaptations, which can be specific to drug type, and their resultant behaviors are modified by various internal and external environmental factors, including stress responsivity, addict mindset, and social setting. Specific gene variants, including variants encoding pharmacological target proteins or genes mediating neuroadaptations, also modify vulnerability at particular stages of addiction. Greater understanding of these interacting factors through laboratory-based and translational studies have the potential to optimize early interventions for the therapy of chronic addictive diseases and to reduce the burden of relapse. Here, we review the molecular neurobiology and genetics of opiate addiction, including heroin and prescription opioids, and cocaine addiction.

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“…Outros mecanismos como ubiquitinação, sumoilação, citrulinação, e ADPribosilação ainda são pouco compreendidos (Tsankova et al, 2007;Yuferov et al, 2010;Wong et al, 2011;Feng, Nestler, 2013).…”

Section: Epigenéticaunclassified

“…Consiste na adição de um grupamento metil (CH3) ao carbono da posição cinco da citosina (C), catalizada pela enzima DNA metiltransferase em dinucleotídeos CpG, que são regiões em que uma citosina (C) precede uma guanina (G) na sequência de DNA ('Cfosfato de ligação G') (Figura 6) (Goldberg et al, 2007;Anier et al, 2010;Yuferov et al, 2010;Robison, Nestler, 2011;Feng, Nestler, 2013;Fragou et al, 2013;Nestler, 2014).…”

Section: Epigenéticaunclassified

“…A metilação nessas regiões está associada ao silenciamento gênico e, quando essas ilhas CpG não estão metiladas, são relacionadas à expressão gênica (Oliveira et al, 2010;Portela, Esteller, 2010;Yuferov et al, 2010). Dinucletídeos encontrados fora de ilhas, em regiões conhecidas como "margens da ilha CpG", discutidas posteriormente, são menos metilados quando comparadas com as ilhas em si (Tsankova et al, 2007;Robison, Nestler, 2011;Nielsen et al, 2012) e também estão associadas com a inativação transcricional.…”

Section: Fonte: Wong Et Al 2011unclassified

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Estudos epigenéticos em dependentes de crack e cocaína: investigação da metilação global do genoma

Camilo¹

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AGRADECIMENTOSAgradeço primeiramente a Deus pela saúde, fé, perseverança e por iluminar o meu caminho durante esta caminhada.Aos meus pais, Ana Maria e Izilmar, por sua história de sucesso na educação dos filhos diante todas as adversidades. Agradeço pela educação que me deram, pela confiança, pelas broncas e por tudo que fizeram por mim com o objetivo de me formar pessoalmente e profissionalmente.Ao meu irmão, Ronaldo, meu melhor amigo, por seus conselhos, ensinamentos e por acreditar em mim e no meu potencial em todos os momentos. Aos meus familiares, por me incentivar nas horas mais difíceis e nas decisões tomadas, por compartilhar e sempre estar ao meu lado ao longo das minhas conquistas.Aos amigos, aos que se foram e aos que permanecem em minha vida até hoje, por todas as palavras de incentivo e persistência.Ao orientador Professor Doutor Homero Vallada, pelo voto de confiança em me acolher como orientanda. Por sua paciência, experiência e ensinamentos nessa jornada. E, principalmente, por incentivar minha maturidade acadêmica e pessoal. À Banca de qualificação, composta pela Profa. Márcia Scazufca, Prof.Guilherme Messas e Prof. Hermano Tavares, pelas sugestões e orientações adequadas ao aprimoramento dessa pesquisa.

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Search for genetic markers and functional variants involved in the development of opiate and cocaine addiction and treatment

Cited by 85 publications

References 295 publications

Analysis of opioid efficacy, tolerance, addiction and dependence from cell culture to human

Analysis of opioid efficacy, tolerance, addiction and dependence from cell culture to human

Opiate addiction and cocaine addiction: underlying molecular neurobiology and genetics

Estudos epigenéticos em dependentes de crack e cocaína: investigação da metilação global do genoma

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