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NrCAM-regulating neural systems and addiction-related behaviors.

ABSTRACT: We have previously shown that a haplotype associated with decreased NrCAM expression in brain is protective against addiction vulnerability for polysubstance abuse in humans and that Nrcam knockout mice do not develop conditioned place preferences for morphine, cocaine or amphetamine. In order to gain insight into NrCAM involvement in addiction vulnerability, which may involve specific neural circuits underlying behavioral characteristics relevant to addiction, we evaluated several behavioral phenotypes in Nrcam knockout mice. Consistent with a potential general reduction in motivational function, Nrcam knockout mice demonstrated less curiosity for novel objects and for an unfamiliar conspecific, showed also less anxiety in the zero maze. Nrcam heterozygote knockout mice reduced alcohol preference and buried fewer marbles in home cage. These observations provide further support for a role of NrCAM in substance abuse including alcoholism vulnerability, possibly through its effects on behavioral traits that may affect addiction vulnerability, including novelty seeking, obsessive compulsion and responses to aversive or anxiety-provoking stimuli. Additionally, in order to prove glutamate homeostasis hypothesis of addiction, we analyzed glutamatergic molecules regulated by NRCAM expression. Glutaminase appears to be involved in NrCAM-related molecular pathway in two different tissues from human and mouse. An inhibitor of the enzyme, prolyl-leucyl-glycinamide, treatment produced, at least, some of the phenotypes of mice shown in alcohol preference and in anxiety-like behavior. Thus, NrCAM could affect addiction-related behaviors via at least partially modulation of some glutamatergic pathways and neural function in brain.

SUBMITTER: Ishiguro H

PROVIDER: S-EPMC3470748 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature

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NrCAM-regulating neural systems and addiction-related behaviors.

Ishiguro Hiroki H Hall Frank S FS Horiuchi Yasue Y Sakurai Takeshi T Hishimoto Akitoyo A Grumet Martin M Uhl George R GR Onaivi Emmanuel S ES Arinami Tadao T

Addiction biology 20120711 3

We have previously shown that a haplotype associated with decreased NrCAM expression in brain is protective against addiction vulnerability for polysubstance abuse in humans and that Nrcam knockout mice do not develop conditioned place preferences for morphine, cocaine or amphetamine. In order to gain insight into NrCAM involvement in addiction vulnerability, which may involve specific neural circuits underlying behavioral characteristics relevant to addiction, we evaluated several behavioral ph ...[more]

PMID: 22780223

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Project description:BackgroundMultiple factors contribute to the etiology of addiction, including genetics, sex, and a number of addiction-related behavioral traits. One behavioral trait where individuals assign incentive salience to food stimuli ("sign-trackers", ST) are more impulsive compared to those that do not ("goal-trackers", GT), as well as more sensitive to drugs and drug stimuli. Furthermore, this GT/ST phenotype predicts differences in other behavioral measures. Recent studies have implicated the gut microbiota as a key regulator of brain and behavior, and have shown that many microbiota-associated changes occur in a sex-dependent manner. However, few studies have examined how the microbiome might influence addiction-related behaviors. To this end, we sought to determine if gut microbiome composition was correlated with addiction-related behaviors determined by the GT/ST phenotype.MethodsOutbred male (N=101) and female (N=101) heterogeneous stock rats underwent a series of behavioral tests measuring impulsivity, attention, reward-learning, incentive salience, and locomotor response. Cecal microbiome composition was estimated using 16S rRNA gene amplicon sequencing. Behavior and microbiome were characterized and correlated with behavioral phenotypes. Robust sex differences were observed in both behavior and microbiome; further analyses were conducted within sex using the pre-established goal/sign-tracking (GT/ST) phenotype and partial least squares differential analysis (PLS-DA) clustered behavioral phenotype.ResultsOverall microbiome composition was not associated to the GT/ST phenotype. However, microbial alpha diversity was significantly decreased in female STs. On the other hand, a measure of impulsivity had many significant correlations to microbiome in both males and females. Several measures of impulsivity were correlated with the genus Barnesiella in females. Female STs had notable correlations between microbiome and attentional deficient. In both males and females, many measures were correlated with the bacterial families Ruminocococcaceae and Lachnospiraceae.ConclusionsThese data demonstrate correlations between several addiction-related behaviors and the microbiome specific to sex.

Project description:IntroductionDepressive emotions can lead to subsequent unhealthy behaviors such as Internet addiction, especially in female adolescents; therefore, studies that examine the relationships among depression, health‑related behaviors, and Internet addiction in female adolescents are warranted.PurposeTo examine (1) the relationship between depression and health-related behaviors and (2) the relationship between depression and Internet addiction.MethodA cross-sectional study design was adopted using a structured questionnaire to measure depression, health-related behaviors, and Internet addiction in female adolescents. The data were collected from students of a junior college in southern Taiwan using convenience sampling to select the participants. The questionnaire was divided into four sections: demographics, the Center for Epidemiologic Studies Depression Scale (CES-D), the Health Promoting Lifestyle Profile (HPLP), and the Internet Addiction Test (IAT).ResultsThe final sample comprised 503 female junior college students, with the participants mainly aged between 15 to 22 years (mean age = 17.30 years, SD = 1.34). Regarding the HPLP scores, the overall score, nutrition subscale score, and self-actualization subscale score were significantly and negatively associated with the CES-D depression score (p < 0.05-0.01). In other words, depression level was lower in students who exhibited more healthy behaviors, put more emphasis on dietary health, and had higher levels of self-admiration and confidence toward life. Regarding the IAT scores, the overall score and six domain scores were all positively associated (p < 0.01) to the CES-D depression score. In other words, the higher an individual's Internet addiction score was, the higher her depression level was.ConclusionsThe results confirmed the relationship between depression, health-related behaviors, and Internet addiction. The cultivation of health-related behaviors may help in lowering depressive symptoms. Teenagers with depression have higher risks of developing Internet addiction, and such addiction is likely to affect their daily functioning.

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NrCAM-regulating neural systems and addiction-related behaviors.

Publications

NrCAM-regulating neural systems and addiction-related behaviors.

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