Dopamine D<sub>2</sub> Receptor Binding, <i>Drd2</i> Expression and the Number of Dopamine Neurons in the BXD Recombinant Inbred Series: Genetic Relationships to Alcohol and Other Drug Associated Phenotypes

Hitzemann, Robert; Hitzemann, Barbara; Rivera, Seth; Gatley, John; Thanos, Peter K.; Shou, Lu Lu Siming; Williams, Robert W.

doi:10.1111/j.1530-0277.2003.tb02713.x

Cited by 37 publications

(16 citation statements)

References 52 publications

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“…Genetic and molecular biological studies have recently linked the Nr-CAM (in both mouse and human populations) with susceptibility to and consequences of addiction (Ishiguro et al 2006;Minana et al 2000), aberrant drug-seeking behavior and dysfunctional brain-based drug reward systems (Hitzemann et al 2003). In support of these contentions, it has been observed that mice with reduced levels of Nr-CAM expression manifest less drug-conditioned place preference (Hall et al 2004;Lin et al 2005).…”

Section: Discussionmentioning

confidence: 99%

Neuronal cell adhesion molecule deletion induces a cognitive and behavioral phenotype reflective of impulsivity

Matzel¹,

Babiarz

Townsend³

et al. 2007

Genes Brain and Behavior

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Cell adhesion molecules, such as neuronal cell adhesion molecule (Nr‐CAM), mediate cell–cell interactions in both the developing and mature nervous system. Neuronal cell adhesion molecule is believed to play a critical role in cell adhesion and migration, axonal growth, guidance, target recognition and synapse formation. Here, wild‐type, heterozygous and Nr‐CAM null mice were assessed on a battery of five learning tasks (Lashley maze, odor discrimination, passive avoidance, spatial water maze and fear conditioning) previously developed to characterize the general learning abilities of laboratory mice. Additionally, all animals were tested on 10 measures of sensory/motor function, emotionality and stress reactivity. We report that the Nr‐CAM deletion had no impact on four of the learning tasks (fear conditioning, spatial water maze, Lashley maze and odor discrimination). However, Nr‐CAM null mice exhibited impaired performance on a task that required animals to suppress movement (passive avoidance). Although Nr‐CAM mutants expressed normal levels of general activity and body weights, they did exhibit an increased propensity to enter stressful areas of novel environments (the center of an open field and the lighted side of a dark/light box), exhibited higher sensitivity to pain (hot plate) and were more sensitive to the aversive effects of foot shock (shock‐induced freezing). This behavioral phenotype suggests that Nr‐CAM does not play a central role in the regulation of general cognitive abilities but may have a critical function in regulating impulsivity and possibly an animal’s susceptibility to drug abuse and addiction.

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Section: Discussionmentioning

confidence: 99%

Neuronal cell adhesion molecule deletion induces a cognitive and behavioral phenotype reflective of impulsivity

Matzel¹,

Babiarz

Townsend³

et al. 2007

Genes Brain and Behavior

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“…Dopamine transmission has been found to modulate multiple facets of impulsivity as well as effort-based discounting (Cardinal et al, 2000;Robbins, 2002;Floresco et al, 2008b). We quantified D1 and D2 dopamine receptor gene expression because such measures, particularly in the prefrontal cortex and striatum, have been demonstrated to be predictive of some aspects of cognition as well as vulnerability to drugs of abuse (Thanos et al, 2001;Hitzemann et al, 2003;Belin et al, 2007;Briand et al, 2008;Loos et al, 2010;Kramer et al, 2011). We found that expression of both D1 and D2 receptor mRNA in specific brain regions was predictive of impulsive action.…”

Section: Data Summarymentioning

confidence: 97%

Prefrontal cortical–striatal dopamine receptor mRNA expression predicts distinct forms of impulsivity

Simon

Beas

Montgomery

et al. 2013

Eur J of Neuroscience

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Variation in dopamine receptor levels has been associated with different facets of impulsivity. To further delineate the neural substrates underlying impulsive action (inability to withhold a prepotent motor response) and impulsive choice (delay aversion), we characterised rats in the Differential Reinforcement of Low Rates of Responding task and a delay discounting task. We also measured performance on an effort-based discounting task. We then assessed D1 and D2 dopamine receptor mRNA expression in subregions of the prefrontal cortex and nucleus accumbens using in situ hybridisation, and compared these data with behavioral performance. Expression of D1 and D2 receptor mRNA in distinct brain regions was predictive of impulsive action. A dissociation within the nucleus accumbens was observed between subregions and receptor subtypes; higher D1 mRNA expression in the shell predicted greater impulsive action, whereas lower D2 mRNA expression in the core predicted greater impulsive action. We also observed a negative correlation between impulsive action and D2 mRNA expression in the prelimbic cortex. Interestingly, a similar relationship was present between impulsive choice and prelimbic cortex D2 mRNA, despite the fact that behavioral indices of impulsive action and impulsive choice were uncorrelated. Finally, we found that both high D1 mRNA expression in the insular cortex and low D2 mRNA expression in the infralimbic cortex were associated with willingness to exert effort for rewards. Notably, dopamine receptor mRNA in these regions was not associated with either facet of impulsivity. The data presented here provide novel molecular and neuroanatomical distinctions between different forms of impulsivity, as well as effort-based decision-making.

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“…In this approach one can index nucleic acid polymorphisms throughout the genome and correlate those polymorphisms with behavioral or biological phenotypes. This approach has proven successful as a first step to identifying polygenes affecting, for example, hippocampal neurobiology (Lassalle et al, 1994), alcohol pharmacology (Rodriguez et al, 1994;Buck et al, 2002) and cocaine pharmacogenetics (Phillips et al, 1998;Jones et al, 1999), dopamine neurochemistry Hitzemann et al, 2003) immunology (Pereira et al, 1997;Hsu et al, 2002) haloperidol sensitivity (Kanes et al, 1996) and other phenotypes.…”

Section: Introductionmentioning

confidence: 99%

Quantitative Genetic Analysis of Ventral Midbrain and Liver Iron in BXD Recombinant Inbred Mice

Jones

Reed

Hitzemann

et al. 2003

Nutritional Neuroscience

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Male and female mice from 15 of the BXD/Ty recombinant inbred strain panel were examined for regional brain and liver iron content. Brain regions included medial prefrontal cortex, nucleus accumbens, caudate-putamen and ventral midbrain. Our focal tissue was the ventral midbrain, containing the ventral tegmentum and substantia nigra. This area contains the perikarya of the dopamine neurons that project to nucleus accumbens and caudate-putamen. Genetic correlations between ventral midbrain and liver iron content were not statistically significant, suggesting that peripheral and central iron regulatory systems are largely independent. Correlations between ventral midbrain iron and iron in the caudate-putamen and nucleus accumbens, but not the prefrontal cortex were moderately high and significant. Ventral midbrain and liver iron contents were subjected to quantitative trait loci analysis to identify associated chromosomal locations. This analysis revealed several suggestive loci for iron content in ventral midbrain but fewer loci for liver. Genetic correlations between ventral midbrain iron and published dopamine functional indices were significant, suggesting a link between ventral midbrain iron status and central dopamine neurobiology. This work shows the value of quantitative genetic analysis in the neurobiology of iron and in showing the close association between ventral midbrain iron and nigrostriatal/mesolimbic dopamine function.

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Dopamine D₂ Receptor Binding, Drd2 Expression and the Number of Dopamine Neurons in the BXD Recombinant Inbred Series: Genetic Relationships to Alcohol and Other Drug Associated Phenotypes

Cited by 37 publications

References 52 publications

Neuronal cell adhesion molecule deletion induces a cognitive and behavioral phenotype reflective of impulsivity

Neuronal cell adhesion molecule deletion induces a cognitive and behavioral phenotype reflective of impulsivity

Prefrontal cortical–striatal dopamine receptor mRNA expression predicts distinct forms of impulsivity

Quantitative Genetic Analysis of Ventral Midbrain and Liver Iron in BXD Recombinant Inbred Mice

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Dopamine D2 Receptor Binding, Drd2 Expression and the Number of Dopamine Neurons in the BXD Recombinant Inbred Series: Genetic Relationships to Alcohol and Other Drug Associated Phenotypes

Cited by 37 publications

References 52 publications

Neuronal cell adhesion molecule deletion induces a cognitive and behavioral phenotype reflective of impulsivity

Neuronal cell adhesion molecule deletion induces a cognitive and behavioral phenotype reflective of impulsivity

Prefrontal cortical–striatal dopamine receptor mRNA expression predicts distinct forms of impulsivity

Quantitative Genetic Analysis of Ventral Midbrain and Liver Iron in BXD Recombinant Inbred Mice

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Product

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Dopamine D₂ Receptor Binding, Drd2 Expression and the Number of Dopamine Neurons in the BXD Recombinant Inbred Series: Genetic Relationships to Alcohol and Other Drug Associated Phenotypes