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Series GSE3016 Query DataSets for GSE3016
Status Public on Jan 26, 2006
Title Gene expression evidence for remodeling of lateral hypothalamic circuitry in cocaine addiction
Organism Rattus norvegicus
Experiment type Expression profiling by array
Summary 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.
Keywords: cocaine addiction
 
Overall design The experimental design for this study comprised three groups of rats (n = 8) with different daily access to a continuous schedule of i.v. cocaine self-administration (0.25 mg per injection): 0 h access per day (drug-naive control rats), 1 h access per day (ShA rats), or 6 h access per day (LgA rats).
Gene expression profiling was then performed for each dissected brain region by using Affymetrix rat neurobiology arrays.
 
Contributor(s) Ahmed SH, Lutjens R, van der Stap LD, Lekic D, Romano-Spica V, Morales M, Koob GF, Repunte-Canonigo V, Sanna PP
Citation(s) 16076954
Submission date Jul 27, 2005
Last update date Jun 21, 2012
Contact name Lena Dina van der Stap
E-mail(s) lenav@scripps.edu
Phone 858-784-7193
Fax 858-784-7077
Organization name The Scripps Research Institute
Department Neuropharmacology
Lab Sanna Lab
Street address 10550 N. Torrey Pines Rd.
City La Jolla
State/province CA
ZIP/Postal code 92037
Country USA
 
Platforms (1)
GPL88 [RN_U34] Affymetrix Rat Neurobiology U34 Array
Samples (63)
GSM93813 nucleus accumbens ctrl replicate 1
GSM93814 nucleus accumbens ctrl replicate 2
GSM93815 nucleus accumbens ctrl replicate 3
Relations
BioProject PRJNA93199

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