Altered sensitivity of CD81-deficient mice to neurobehavioral effects of cocaine

Michna, Laura; Verca, Maria S. Brenz; Widmer, David A.J.; Chen, Stephen H.; Lee, James; Rogove, Jon; Zhou, Ran; Tsitsikov, Erdyni; Miescher, G; Dreyer, Jean-Luc; Wagner, George C.

doi:10.1016/s0169-328x(01)00092-4

Cited by 21 publications

(17 citation statements)

References 19 publications

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“…61 CD81 is increased in the NAC by cocaine administration, and has been shown to mediate some of the behavioral activating effects of cocaine. [62][63][64] Our data show that CD81 is a Category I gene, changed in expression in the AMY in all three alcohol-related experimental paradigms we studied. While there seems to be an increase in the expression of CD81 in alcohol-preferring rats at baseline, of note there is a strong decrease in its expression in the NAC following ICSA administration of alcohol in the VTA (Table 1), opposite to the effects of systemic administration of cocaine.…”

Section: Fibronectinmentioning

confidence: 58%

Candidate genes, pathways and mechanisms for alcoholism: an expanded convergent functional genomics approach

Bertsch

Strother

et al. 2006

Pharmacogenomics J

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We describe a comprehensive translational approach for identifying candidate genes for alcoholism. The approach relies on the cross-matching of animal model brain gene expression data with human genetic linkage data, as well as human tissue data and biological roles data, an approach termed convergent functional genomics. An analysis of three animal model paradigms, based on inbred alcohol-preferring (iP) and alcohol-non-preferring (iNP) rats, and their response to treatments with alcohol, was used. A comprehensive analysis of microarray gene expression data from five key brain regions (frontal cortex, amygdala, caudate-putamen, nucleus accumbens and hippocampus) was carried out. The Bayesian-like integration of multiple independent lines of evidence, each by itself lacking sufficient discriminatory power, led to the identification of high probability candidate genes, pathways and mechanisms for alcoholism. These data reveal that alcohol has pleiotropic effects on multiple systems, which may explain the diverse neuropsychiatric and medical pathology in alcoholism. Some of the pathways identified suggest avenues for pharmacotherapy of alcoholism with existing agents, such as angiotensin-converting enzyme (ACE) inhibitors. Experiments we carried out in alcohol-preferring rats with an ACE inhibitor show a marked modulation of alcohol intake. Other pathways are new potential targets for drug development. The emergent overall picture is that physical and physiological robustness may permit alcohol-preferring individuals to withstand the aversive effects of alcohol. In conjunction with a higher reactivity to its rewarding effects, they may able to ingest enough of this nonspecific drug for a strong hedonic and addictive effect to occur.

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Section: Fibronectinmentioning

confidence: 58%

Candidate genes, pathways and mechanisms for alcoholism: an expanded convergent functional genomics approach

Bertsch

Strother

et al. 2006

Pharmacogenomics J

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“…Enhanced cell adhesion might make these synapses less adaptable and impede the proper formation and reinforcement of learning-specific connections. Previous research has reported upregulations in genes associated with cell adhesion within the nucleus accumbens Freeman et al, 2001) and ventral tegmental area, with links to behaviors such as sensitization (Michna et al, 2001;Bahi et al, 2004).…”

Section: Effects Of Early Developmental Exposure To Cocaine On Gene Ementioning

confidence: 99%

Altered Attention and Prefrontal Cortex Gene Expression in Rats after Binge-Like Exposure to Cocaine during Adolescence

Black¹,

Maclaren²,

Naydenov³

et al. 2006

J. Neurosci.

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Illicit use of drugs frequently begins and escalates during adolescence, with long-term adverse consequences. Because it is increasingly accepted that neural development continues through adolescence, addiction research has become more invested in understanding the behavioral and molecular consequences of early exposure to drugs of abuse. In a novel binge administration paradigm designed to model the pattern of human adolescent drug use, we administered ascending doses of cocaine or saline during a 12-d developmental period [postnatal day 35 (P35) to P46] corresponding to human adolescence. During adulthood (P70), rats treated with this regimen displayed increased responsiveness to the stimulant effects of cocaine. Adult rats also displayed abnormally rapid shifts in attention when performing an attentional set-shifting task, which measures the ability to shift attention between stimuli and whose performance requires an intact prefrontal cortex (PFC). Treatment with cocaine during adolescence also caused acute alterations in the expression of genes encoding cell adhesion molecules and transcription factors within the PFC. Furthermore, we observed decreases in histone methylation, which may indicate a role for chromatin remodeling in the observed changes in gene expression patterns. These findings suggest that exposure to cocaine during adolescence has far-reaching molecular and behavioral consequences in the rat PFC that develop over time and endure long after drug administration has ceased.

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“…Nevertheless little is known about cell surface molecules involved in neuroadaptations after drug intake. Strong induction of a surface tetraspanin protein, CD81, has been described (Michna et al, 2001, Halladay et al, 2000, Brenz-Verca et al, 2001, Bahi et al, 2004. Also specific axon guidance cues, such as EphB1 and ephrin-B2, are expressed after challenges with psychomotor stimulants, (Zhou, 1998;Yue et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

Cocaine-induced expression changes of axon guidance molecules in the adult rat brain

Bahí

Dreyer

2005

Molecular and Cellular Neuroscience

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Administration of drugs of abuse induces strong molecular adaptations and plasticity within the mesolimbic dopamine (DA) system, a pathway essential for reward-seeking behavior. Little is known about the specific targets involved in this neuroadaptation process, but there are indications that cocaine and other drugs of abuse share the ability to alter the morphology of neuronal dendrites and spines, the primary site of excitatory synapses in the brain. Axon guidance molecules, the very molecular cues that regulate the formation of axon-target connections during development, may mediate these alterations. To test this hypothesis, we investigated mRNA expression changes of 39 axon guidance molecules, including 17 Semaphorins, 12 Ephs, 8 Ephrins and 2 neuropilins in the mesolimbic dopamine system of cocaine-treated animals under different paradigms by mean of DNA-Microarray and quantitative real-time PCR. In all cases, strong changes in gene expression are observed, yielding to up or down-regulation of these axon guidance molecules. Our data suggest that cocaine treatment induces activation of a complex program of synaptic rearrangements, which may partly recapitulate the plastic changes occurring during development, and may underlie the important neuroplastic adaptations that occur in the reward-and memory-related brain centers following drug action. We conclude that in some brain regions, exposure to psychomotor-stimulant drugs produce expression changes in axon guidance molecules, which may contribute to cognitive deficits associated with drug abuse.2

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Altered sensitivity of CD81-deficient mice to neurobehavioral effects of cocaine

Cited by 21 publications

References 19 publications

Candidate genes, pathways and mechanisms for alcoholism: an expanded convergent functional genomics approach

Candidate genes, pathways and mechanisms for alcoholism: an expanded convergent functional genomics approach

Altered Attention and Prefrontal Cortex Gene Expression in Rats after Binge-Like Exposure to Cocaine during Adolescence

Cocaine-induced expression changes of axon guidance molecules in the adult rat brain

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