Mesocorticolimbic monoamine correlates of methamphetamine sensitization and motivation

Kevin D. Lominac, Courtney L. McKenna, Lisa M. Schwartz, Paige N. Ruiz, Melissa G. Wroten, Bailey W. Miller, John J. Holloway, Katherine O. Travis, Ganesh Rajasekar, Dan Maliniak, Andrew B. Thompson, Lawrence E. Urman, Tamara J. Phillips, Karen K. Szumlinski

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31 Scopus citations


Methamphetamine (MA) is a highly addictive psychomotor stimulant, with life-time prevalence rates of abuse ranging from 5-10% world-wide. Yet, a paucity of research exists regarding MA addiction vulnerability/resiliency and neurobiological mediators of the transition to addiction that might occur upon repeated low-dose MA exposure, more characteristic of early drug use. As stimulant-elicited neuroplasticity within dopamine neurons innervating the nucleus accumbens (NAC) and prefrontal cortex (PFC) is theorized as central for addiction-related behavioral anomalies, we used a multi-disciplinary research approach in mice to examine the interactions between sub-toxic MA dosing, motivation for MA and mesocorticolimbic monoamines. Biochemical studies of C57BL/6J (B6) mice revealed short- (1 day), as well as longer-term (21 days), changes in extracellular dopamine, DAT and/or D2 receptors during withdrawal from 10, once daily, 2 mg/kg MA injections. Follow-up biochemical studies conducted in mice selectively bred for high vs. low MA drinking (respectively, MAHDR vs. MALDR mice), provided novel support for anomalies in mesocorticolimbic dopamine as a correlate of genetic vulnerability to high MA intake. Finally, neuropharmacological targeting of NAC dopamine in MA-treated B6 mice demonstrated a bi-directional regulation of MA-induced place-conditioning. These results extend extant literature for MA neurotoxicity by demonstrating that even subchronic exposure to relatively low MA doses are sufficient to elicit relatively long-lasting changes in mesocorticolimbic dopamine and that drug-induced or idiopathic anomalies in mesocorticolimbic dopamine may underpin vulnerability/resiliency to MA addiction.

Original languageEnglish (US)
Article number70
JournalFrontiers in Systems Neuroscience
Issue numberMAY
StatePublished - May 7 2014


  • Addiction vulnerability
  • Dopamine
  • Methamphetamine
  • Nucleus accumbens
  • Prefrontal cortex
  • Sensitization
  • Serotonin

ASJC Scopus subject areas

  • Neuroscience (miscellaneous)
  • Developmental Neuroscience
  • Cognitive Neuroscience
  • Cellular and Molecular Neuroscience


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