The brain gene expression profile of dopamine D2/D3 receptors and associated signaling proteins following amphetamine self-administration

Neuroscience. 2015 Oct 29;307:253-61. doi: 10.1016/j.neuroscience.2015.08.053. Epub 2015 Aug 28.


Persistent neuroadaptations following chronic psychostimulant exposure include reduced striatal dopamine D2 receptor (D2R) levels. The signaling of D2Rs is initiated by Gαi/o proteins and terminated by regulator of G protein signaling (RGS) proteins. The purpose of this study is to examine the association of the drug taking behavior and gene expression profile of D2/D3Rs, and their associated signaling proteins in the ventral tegmental area (VTA) and nucleus accumbens (NAc) using a rodent model of amphetamine (AMPH) self-administration. Rats were allowed to self-administer AMPH (0.187 mg/kg/infusion for a maximum of 40 injections in 6h daily sessions) for 5 days during which rats showed an escalated rate of AMPH intake across days. AMPH self-administration induced profound brain region-dependent alterations of the targeted genes. There was a positive correlation of the messenger ribonucleic acid (mRNA) levels of RGS10 between the VTA and the NAc in the control animals, which was abolished by AMPH self-administration. AMPH self-administration also produced a negative correlation of the mRNA levels of RGS7 and RGS19 between the two brain regions, which was not present in the control group. Furthermore, AMPH taking behavior was associated with changes in certain gene expression levels. The mRNA levels of RGS2 and RGS4 in both the VTA and NAc were positively correlated with the rate of AMPH intake. Additionally, the rate of AMPH intake was also positively correlated with RGS10 and negatively correlated with RGS17 and the short form of D2Rs mRNA level in the VTA. Although there were significant changes in the mRNA levels of RGS7 and RGS8 in the NAc, none of these measures were correlated with the rate of AMPH intake. The present study suggested that short-term AMPH self-administration produced pronounced changes in the VTA that were more associated with AMPH taking behavior than changes in the NAc.

Keywords: GPCR: G protein-coupled receptor; Gαi/o proteins; RGS proteins; amphetamine self-administration; dopamine D2/D3 receptors; gene expression.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amphetamine / administration & dosage*
  • Analysis of Variance
  • Animals
  • Brain / drug effects*
  • Central Nervous System Stimulants / administration & dosage*
  • Gene Expression Regulation / drug effects
  • Male
  • RGS Proteins / genetics
  • RGS Proteins / metabolism*
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Dopamine D2 / genetics
  • Receptors, Dopamine D2 / metabolism*
  • Receptors, Dopamine D3 / genetics
  • Receptors, Dopamine D3 / metabolism*
  • Self Administration
  • Statistics as Topic
  • Transcriptome


  • Central Nervous System Stimulants
  • RGS Proteins
  • RNA, Messenger
  • Receptors, Dopamine D2
  • Receptors, Dopamine D3
  • Amphetamine