AUTHOR=Lominac Kevin D. , McKenna Courtney L. , Schwartz Lisa M. , Ruiz Paige N. , Wroten Melissa G. , Miller Bailey W. , Holloway John J. , Travis Katherine O. , Rajasekar Ganesh , Maliniak Dan , Thompson Andrew B. , Urman Lawrence E. , Phillips Tamara J. , Szumlinski Karen K. TITLE=Mesocorticolimbic monoamine correlates of methamphetamine sensitization and motivation JOURNAL=Frontiers in Systems Neuroscience VOLUME=8 YEAR=2014 URL=https://www.frontiersin.org/journals/systems-neuroscience/articles/10.3389/fnsys.2014.00070 DOI=10.3389/fnsys.2014.00070 ISSN=1662-5137 ABSTRACT=

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.