Gene expression in accumbens GABA neurons from inbred rats with different drug-taking behavior

Burt Sharp, Hao Chen, S. Gong, X. Wu, Z. Liu, K. Hiler, W. L. Taylor, S. G. Matta

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Inbred Lewis and Fisher 344 rat strains differ greatly in drug self-administration; Lewis rats operantly self-administer drugs of abuse including nicotine, whereas Fisher self-administer poorly. As shown herein, operant food self-administration is similar. On the basis of their pivotal role in drug reward, we hypothesized that differences in basal gene expression in GABAergic neurons projecting from nucleus accumbens (NAcc) to ventral pallidum (VP) play a role in vulnerability to drug-taking behavior. The transcriptomes of NAcc shell-VP GABAergic neurons from these two strains were analyzed in adolescents, using a multidisciplinary approach that combined stereotaxic ionotophoretic brain microinjections, laser-capture microdissection (LCM) and microarray measurement of transcripts. Laser-capture microdissection enriched the gene transcripts detected in gamma-aminobutyric acid (GABA) neurons compared to the residual NAcc tissue: a ratio of neuron/residual >1 and false discovery rate (FDR) <5% yielded 6623 transcripts, whereas a ratio of >3 yielded 3514. Strain-dependent differences in gene expression within GABA neurons were identified; 322 vs. 60 transcripts showed 1.5-fold vs. 2-fold differences in expression (FDR < 5%). Classification by gene ontology showed that these 322 transcripts were widely distributed, without categorical enrichment. This is most consistent with a global change in GABA neuron function. Literature mining by Chilibot found 38 genes related to synaptic plasticity, signaling and gene transcription, all of which determine drug abuse; 33 genes have no known association with addiction or nicotine. In Lewis rats, upregulation of Mint-1, Cask, CamkII , Ncam1, Vsnl1, Hpcal1 and Car8 indicates that these transcripts likely contribute to altered signaling and synaptic function in NAcc GABA projection neurons to VP.

Original languageEnglish (US)
Pages (from-to)778-788
Number of pages11
JournalGenes, Brain and Behavior
Volume10
Issue number7
DOIs
StatePublished - Oct 1 2011

Fingerprint

gamma-Aminobutyric Acid
Nucleus Accumbens
Gene Expression
Neurons
Laser Capture Microdissection
GABAergic Neurons
Self Administration
Pharmaceutical Preparations
Nicotine
Genes
Mentha
Gene Ontology
Neuronal Plasticity
Inbred F344 Rats
Microinjections
Street Drugs
Reward
Transcriptome
Substance-Related Disorders
Up-Regulation

All Science Journal Classification (ASJC) codes

  • Genetics
  • Neurology
  • Behavioral Neuroscience

Cite this

Gene expression in accumbens GABA neurons from inbred rats with different drug-taking behavior. / Sharp, Burt; Chen, Hao; Gong, S.; Wu, X.; Liu, Z.; Hiler, K.; Taylor, W. L.; Matta, S. G.

In: Genes, Brain and Behavior, Vol. 10, No. 7, 01.10.2011, p. 778-788.

Research output: Contribution to journalArticle

Sharp, Burt ; Chen, Hao ; Gong, S. ; Wu, X. ; Liu, Z. ; Hiler, K. ; Taylor, W. L. ; Matta, S. G. / Gene expression in accumbens GABA neurons from inbred rats with different drug-taking behavior. In: Genes, Brain and Behavior. 2011 ; Vol. 10, No. 7. pp. 778-788.
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