Gene expression evidence for remodeling of lateral hypothalamic circuitry in cocaine addiction
| العنوان: | Gene expression evidence for remodeling of lateral hypothalamic circuitry in cocaine addiction |
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| المؤلفون: | Robert Lutjens, Lena D. van der Stap, Pietro Paolo Sanna, Dusan Lekic, Vincenzo Romano-Spica, George F. Koob, Serge H. Ahmed, Vez Repunte-Canonigo, Marisela Morales |
| المصدر: | Proceedings of the National Academy of Sciences. 102:11533-11538 |
| بيانات النشر: | Proceedings of the National Academy of Sciences, 2005. |
| سنة النشر: | 2005 |
| مصطلحات موضوعية: | medicine.medical_specialty, Lateral hypothalamus, Synaptogenesis, Gene Expression, Neurotransmission, Biology, Nucleus accumbens, Amygdala, Cocaine-Related Disorders, Cocaine, Internal medicine, medicine, Animals, Rats, Wistar, Prefrontal cortex, Oligonucleotide Array Sequence Analysis, Neuronal Plasticity, Multidisciplinary, Reverse Transcriptase Polymerase Chain Reaction, Gene Expression Profiling, Brain, Biological Sciences, Rats, Ventral tegmental area, medicine.anatomical_structure, Endocrinology, Synapses, Synaptic plasticity, Female |
| الوصف: | By using high-density oligonucleotide arrays, we profiled gene expression in reward-related brain regions of rats that developed escalated cocaine intake after extended access to cocaine (6 h per day). Rats allowed restricted daily access to cocaine (only 1 h) that displayed a stable level of cocaine intake and cocaine naive rats were used for controls. Four analysis methods were compared: Affymetrix microarray suite 4 and microarray suite 5 , which use perfect-match-minus-mismatch models, and dchip and rma , which use perfect-match-only models to generate expression values. Results were validated by RT-PCR in individual animals from an independent replication of the experiment. A small number of genes was associated with escalated cocaine intake (ESC genes). Unexpectedly, of the brain regions examined [prefrontal cortex, nucleus accumbens, septum, lateral hypothalamus (LH), amygdala, and ventral tegmental area], the LH was the most transcriptionally responsive in escalation of cocaine intake. Most of the ESC genes identified are also expressed during synaptogenesis and synaptic plasticity and include genes that code for several presynaptic and postsynaptic proteins involved in neurotransmission. These results suggest that LH intrinsic circuitry undergoes a structural reorganization during escalation of cocaine use. This remodeling of LH circuitry could contribute to the chronic deficit in reward function that has been hypothesized to drive the transition to drug addiction. Results also support the value of using multiple analysis strategies to identify the most robust changes in gene expression and to compensate for the biases that affect each strategy. |
| تدمد: | 1091-6490 0027-8424 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7534b6616ad7cc163cbebb12755efae2 https://doi.org/10.1073/pnas.0504438102 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....7534b6616ad7cc163cbebb12755efae2 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10916490 00278424 |
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