Systems Level Neuroplasticity in Drug Addiction.

Systems Level Neuroplasticity in Drug Addiction.

Cold Spring Harb Perspect Med. 2013 Apr 11;
Feltenstein MW, See RE

Drug addiction is a chronic relapsing disorder for which research has been dedicated to understand the various factors that contribute to development, loss of control, and persistence of compulsive addictive behaviors. In this review, we provide a broad overview of various theories of addiction, drugs of abuse, and the neurobiology involved across the addiction cycle. Specific focus is devoted to the role of the mesolimbic pathway in acute drug reinforcement and occasional drug use, the mesocortical pathway and associated areas (e.g., the dorsal striatum) in escalation/dependence, and the involvement of these pathways and associated circuits in mediating conditioned responses, drug craving, and loss of behavioral control thought to underlie withdrawal and relapse. With a better understanding of the neurobiological factors that underlie drug addiction, continued preclinical and clinical research will aid in the development of novel therapeutic interventions that can serve as effective long-term treatment strategies for drug-dependent individuals. HubMed – addiction


Genetic variation of the ghrelin signalling system in individuals with amphetamine dependence.

PLoS One. 2013; 8(4): e61242
Suchankova P, Jerlhag E, Jayaram-Lindström N, Nilsson S, Toren K, Rosengren A, Engel JA, Franck J

The development of amphetamine dependence largely depends on the effects of amphetamine in the brain reward systems. Ghrelin, an orexigenic peptide, activates the reward systems and is required for reward induced by alcohol, nicotine, cocaine and amphetamine in mice. Human genetic studies have shown that polymorphisms in the pre-proghrelin (GHRL) as well as GHS-R1A (GHSR) genes are associated with high alcohol consumption, increased weight and smoking in males. Since the heritability factor underlying drug dependence is shared between different drugs of abuse, we here examine the association between single nucleotide polymorphisms (SNPs) and haplotypes in the GHRL and GHSR, and amphetamine dependence. GHRL and GHSR SNPs were genotyped in Swedish amphetamine dependent individuals (n?=?104) and controls from the general population (n?=?310). A case-control analysis was performed and SNPs and haplotypes were additionally tested for association against Addiction Severity Interview (ASI) composite score of drug use. The minor G-allele of the GHSR SNP rs2948694, was more common among amphetamine dependent individuals when compared to controls (pc ?=?0.02). A significant association between the GHRL SNP rs4684677 and ASI composite score of drug use was also reported (pc ?=?0.03). The haplotype analysis did not add to the information given by the individual polymorphisms. Although genetic variability of the ghrelin signalling system is not a diagnostic marker for amphetamine dependence and problem severity of drug use, the present results strengthen the notion that ghrelin and its receptor may be involved in the development of addictive behaviours and may thus serve as suitable targets for new treatments of such disorders. HubMed – addiction


Maturation of the adolescent brain.

Neuropsychiatr Dis Treat. 2013; 9: 449-61
Arain M, Haque M, Johal L, Mathur P, Nel W, Rais A, Sandhu R, Sharma S

Adolescence is the developmental epoch during which children become adults – intellectually, physically, hormonally, and socially. Adolescence is a tumultuous time, full of changes and transformations. The pubertal transition to adulthood involves both gonadal and behavioral maturation. Magnetic resonance imaging studies have discovered that myelinogenesis, required for proper insulation and efficient neurocybernetics, continues from childhood and the brain’s region-specific neurocircuitry remains structurally and functionally vulnerable to impulsive sex, food, and sleep habits. The maturation of the adolescent brain is also influenced by heredity, environment, and sex hormones (estrogen, progesterone, and testosterone), which play a crucial role in myelination. Furthermore, glutamatergic neurotransmission predominates, whereas gamma-aminobutyric acid neurotransmission remains under construction, and this might be responsible for immature and impulsive behavior and neurobehavioral excitement during adolescent life. The adolescent population is highly vulnerable to driving under the influence of alcohol and social maladjustments due to an immature limbic system and prefrontal cortex. Synaptic plasticity and the release of neurotransmitters may also be influenced by environmental neurotoxins and drugs of abuse including cigarettes, caffeine, and alcohol during adolescence. Adolescents may become involved with offensive crimes, irresponsible behavior, unprotected sex, juvenile courts, or even prison. According to a report by the Centers for Disease Control and Prevention, the major cause of death among the teenage population is due to injury and violence related to sex and substance abuse. Prenatal neglect, cigarette smoking, and alcohol consumption may also significantly impact maturation of the adolescent brain. Pharmacological interventions to regulate adolescent behavior have been attempted with limited success. Since several factors, including age, sex, disease, nutritional status, and substance abuse have a significant impact on the maturation of the adolescent brain, we have highlighted the influence of these clinically significant and socially important aspects in this report. HubMed – addiction


Medicaid care management: Description of high-cost addictions treatment clients.

J Subst Abuse Treat. 2013 Apr 8;
Neighbors CJ, Sun Y, Yerneni R, Tesiny E, Burke C, Bardsley L, McDonald R, Morgenstern J

High utilizers of alcohol and other drug treatment (AODTx) services are a priority for healthcare cost control. We examine characteristics of Medicaid-funded AODTx clients, comparing three groups: individuals <90th percentile of AODTx expenditures (n=41,054); high-cost clients in the top decile of AODTx expenditures (HC; n=5,718); and 1760 enrollees in a chronic care management (CM) program for HC clients implemented in 22 counties in New York State. Medicaid and state AODTx registry databases were combined to draw demographic, clinical, social needs and treatment history data. HC clients accounted for 49% of AODTx costs funded by Medicaid. As expected, HC clients had significant social welfare needs, comorbid medical and psychiatric conditions, and use of inpatient services. The CM program was successful in enrolling some high-needs, high-cost clients but faced barriers to reaching the most costly and disengaged individuals. HubMed – addiction



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