Psychostimulant-Induced Neuroadaptations in Nucleus Accumbens AMPA Receptor Transmission.
Psychostimulant-Induced Neuroadaptations in Nucleus Accumbens AMPA Receptor Transmission.
Filed under: Addiction Rehab
Cold Spring Harb Perspect Med. 2012 Dec 10;
Pierce RC, Wolf ME
Medium spiny neurons of the nucleus accumbens serve as the interface between corticolimbic regions that elicit and modulate motivated behaviors, including those related to drugs of abuse, and motor regions responsible for their execution. Medium spiny neurons are excited primarily by AMPA-type glutamate receptors, making AMPA receptor transmission in the accumbens a key regulatory point for addictive behaviors. In animal models of cocaine addiction, changes in the strength of AMPA receptor transmission onto accumbens medium spiny neurons have been shown to underlie cocaine-induced behavioral adaptations related to cocaine seeking. Here we review changes in AMPA receptor levels and subunit composition that occur after discontinuing different types of cocaine exposure, as well as changes elicited by cocaine reexposure following abstinence or extinction. Signaling pathways that regulate these cocaine-induced adaptations will also be considered, as they represent potential targets for addiction pharmacotherapies.
HubMed – addiction
Conversation with Robert Voas.
Filed under: Addiction Rehab
Addiction. 2012 Dec 11;
The heritability of oxycodone reward and concomitant phenotypes in a LG/J?×?SM/J mouse advanced intercross line.
Filed under: Addiction Rehab
Addict Biol. 2012 Dec 12;
Bryant CD, Guido MA, Kole LA, Cheng R
The rewarding property of opioids likely contributes to their abuse potential. Therefore, determining the genetic basis of opioid reward could aid in understanding the neurobiological mechanisms of opioid addiction, provided that it is a heritable trait. Here, we characterized the rewarding property of the widely abused prescription opioid oxycodone (OXY) in the conditioned place preference (CPP) assay using LG/J and SM/J parental inbred mouse strains and 17 parent-offspring families of a LG/J?×?SM/J F(47) /F(48) advanced intercross line (AIL). Following OXY training (5?mg/kg, i.p.), SM/J mice and AIL mice, but not LG/J mice, showed an increase in preference for the OXY-paired side, suggesting a genetic basis for OXY-CPP. SM/J mice showed greater locomotor activity than LG/J mice in response to both saline and OXY. LG/J, SM/J, and AIL mice all exhibited robust OXY-induced locomotor sensitization. Narrow-sense heritability (h(2) ) estimates of the phenotypes using linear regression and maximum likelihood estimation showed good agreement (r?=?0.91). OXY-CPP was clearly not a heritable trait whereas drug-free- and OXY-induced locomotor activity and sensitization were significantly and sometimes highly heritable (h(2) ?=?0.30-0.84). Interestingly, the number of transitions between the saline- and OXY-paired sides emerged as a reliably heritable trait following OXY training (h(2) ?=?0.46-0.66) and could represent a genetic component of drug-seeking behavior. Thus, although OXY-CPP does not appear to be amenable to genome-wide quantitative trait locus mapping, this protocol will be useful for mapping other traits potentially relevant to opioid abuse.
HubMed – addiction
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