DESCRIPTION:

Differentially expressed genes in the striatum of male, group housed 129Sv/Jae S4 mice (8-10 months old) following 7 days of D-amphetamine exposure. Genes in bold font were downregulated and genes in regular font were upregulated in the amphetamine- treated group. Gene expression was evaluated via RNA-seq. Genes with RPKM sequence counts fewer than 1 in all samples were removed. Data taken from Table 2. Values presented are ""1"" for presence."

LABEL:

mouse D-amphetamine 7 d

SCORE TYPE:

Binary

DATE ADDED:

2021-07-01

DATE UPDATED:

2024-04-25

SPECIES:

AUTHORS:

Jill R Crittenden, Theresa A Gipson, Anne C Smith, Hilary A Bowden, Ferah Yildirim, Kyle B Fischer, Michael Yim, David E Housman, Ann M Graybiel

TITLE:

Striatal transcriptome changes linked to drug-induced repetitive behaviors.

JOURNAL:

The European journal of neuroscience 04 2021, Vol 53, pp. 2450-2468

ABSTRACT:

Disruptive or excessive repetitive motor patterns (stereotypies) are cardinal symptoms in numerous neuropsychiatric disorders. Stereotypies are also evoked by psychomotor stimulants such as amphetamine. The acquisition of motor sequences is paralleled by changes in activity patterns in the striatum, and stereotypies have been linked to abnormal plasticity in these reinforcement-related circuits. Here, we designed experiments in mice to identify transcriptomic changes that underlie striatal plasticity occurring alongside the development of drug-induced stereotypic behavior. We identified three schedules of amphetamine treatment inducing different degrees of stereotypy and used bulk RNAseq to compare striatal gene expression changes among groups of mice treated with the different drug-dose schedules and vehicle-treated, cage-mate controls. Mice were identified as naïve, sensitized, or tolerant to drug-induced stereotypy. All drug-treated groups exhibited expression changes in genes that encode members of the extracellular signal-regulated kinase (ERK) cascades known to regulate psychomotor stimulant responses. In the sensitized group with the most prolonged stereotypy, we found dysregulation of 20 genes that were not changed in other groups. Gene set enrichment analysis indicated highly significant overlap with genes regulated by neuregulin 1 (Nrg1). Nrg1 is known to be a schizophrenia and autism susceptibility gene that encodes a ligand for Erb-B receptors, which are involved in neuronal migration, myelination, and cell survival, including that of dopamine-containing neurons. Stimulant abuse is a risk factor for schizophrenia onset, and these two disorders share behavioral stereotypy phenotypes. Our results raise the possibility that drug-induced sensitization of the Nrg1 signaling pathway might underlie these links. PUBMED: 33759265
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