Addiction Is a Brain Disease, and It Matters

Leshner, Alan I.

doi:10.1176/foc.1.2.190

Cited by 299 publications

(382 citation statements)

References 14 publications

Supporting

Mentioning

356

Contrasting

Unclassified

Order By: Relevance

“…Intracellular mechanisms of neurotoxicity induced by amphetamines, cocaine or heroin Since addiction may be considered a brain disease (Leshner, 1997), neurotoxicity may underlie some of the effects of the drugs. The Interagency Committee on Neurotoxicology defined neurotoxicity as a broad concept, including any adverse effect on the structure or function of the central and/or peripheral nervous system by a biological, chemical or physical agent.…”

Section: 4mentioning

confidence: 99%

Cellular and molecular mechanisms involved in the neurotoxicity of opioid and psychostimulant drugs

Cunha‐Oliveira

Rego

Oliveira

2008

Brain Research Reviews

193

136

View full text Add to dashboard Cite

show abstract

Section: 4mentioning

confidence: 99%

Cellular and molecular mechanisms involved in the neurotoxicity of opioid and psychostimulant drugs

Cunha‐Oliveira

Rego

Oliveira

2008

Brain Research Reviews

193

136

View full text Add to dashboard Cite

show abstract

“…A central problem in treating drug addiction is the vulnerability to relapse during abstinence (Leshner 1997), and a better understanding of the underlying mechanisms of relapse may identify important therapeutic targets and suggest novel treatments. Towards this goal, animal models of relapse were developed that identified triggers for reinstatement of drug selfadministration Stewart 1981, 1983;Gerber and Stretch 1975;Stretch and Gerber 1973).…”

Section: Introductionmentioning

confidence: 99%

Stress-induced reinstatement of cocaine seeking is mediated by the kappa opioid system

2008

View full text Add to dashboard Cite

Introduction-Prior activation of the kappa opioid system by repeated stress or agonist administration has been previously shown to potentiate the rewarding properties of subsequently administered cocaine. In the present study, intermittent and uncontrollable footshock, a single session of forced swim, or acute administration of the kappa agonist U50,488 (5 mg/kg) were found to reinstate place preference in mice previously conditioned with cocaine (15 mg/kg) and subsequently extinguished by repeated training sessions without drug.

show abstract

“…Drug addiction is characterized by the compulsive seeking and taking of drugs despite adverse consequences (Leshner, 1997). A cardinal feature of this brain disease is that it is long-lasting (Koob et al, 1998;White and Kalivas, 1998;Berke and Hyman, 2000;Nestler, 2001;Hyman and Malenka, 2001).…”

Section: Introductionmentioning

confidence: 99%

Repeated Cocaine Administration Induces Gene Expression Changes through the Dopamine D1 Receptors

Zhang

Tang

et al. 2005

Neuropsychopharmacol

View full text Add to dashboard Cite

Drug addiction involves compulsive drug-seeking and drug-taking despite known adverse consequences. The enduring nature of drug addiction suggests that repeated exposure to abused drugs leads to stable alterations that likely involve changes in gene expression in the brain. The dopamine D1 receptor has been shown to mediate the long-term behavioral effects of cocaine. To examine how the persistent behavioral effects of cocaine correlate with underlying changes in gene expression, we have used D1 receptor mutant and wild-type mice to identify chronic cocaine-induced gene expression changes mediated via the D1 receptors. We focused on the caudoputamen and nucleus accumbens, two key brain regions that mediate the long-term effects of cocaine. Our analyses demonstrate that repeated cocaine administration induces changes in the expression of 109 genes, including those encoding the stromal cell-derived factor 1, insulin-like growth factor binding protein 6, sigma 1 receptor, regulators of G-protein signaling protein 4, Wnt1 responsive Cdc42 homolog, Ca 2 þ /calmodulin-dependent protein kinase II a subunit, and cyclin D2, via the D1 receptors. Moreover, the seven genes contain AP-1 binding sites in their promoter regions. These results suggest that genes encoding certain extracellular factors, membrane receptors and modulators, and intracellular signaling molecules, among others, are regulated by cocaine via the D1 receptor, and these AP-1 transcription complex-regulated genes might contribute to persistent cocaine-induced behavioral changes.

show abstract

Addiction Is a Brain Disease, and It Matters

Cited by 299 publications

References 14 publications

Cellular and molecular mechanisms involved in the neurotoxicity of opioid and psychostimulant drugs

Cellular and molecular mechanisms involved in the neurotoxicity of opioid and psychostimulant drugs

Stress-induced reinstatement of cocaine seeking is mediated by the kappa opioid system

Repeated Cocaine Administration Induces Gene Expression Changes through the Dopamine D1 Receptors

Contact Info

Product

Resources

About