Mesocorticolimbic monoamine correlates of methamphetamine sensitization and motivation
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 up...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2014-05-01
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| Series: | Frontiers in Systems Neuroscience |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fnsys.2014.00070/full |
| _version_ | 1819054972208152576 |
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| author | 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 eRajasekar Dan eMaliniak Andrew B Thompson Lawrence E Urman Tamara ePhillips Karen K Szumlinski |
| author_facet | 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 eRajasekar Dan eMaliniak Andrew B Thompson Lawrence E Urman Tamara ePhillips Karen K Szumlinski |
| author_sort | Kevin D Lominac |
| collection | DOAJ |
| description | 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 versus 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. |
| first_indexed | 2024-12-21T13:00:07Z |
| format | Article |
| id | doaj.art-8cbae492ae28499f97fa7dade4c22b96 |
| institution | Directory Open Access Journal |
| issn | 1662-5137 |
| language | English |
| last_indexed | 2024-12-21T13:00:07Z |
| publishDate | 2014-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Systems Neuroscience |
| spelling | doaj.art-8cbae492ae28499f97fa7dade4c22b962022-12-21T19:03:12ZengFrontiers Media S.A.Frontiers in Systems Neuroscience1662-51372014-05-01810.3389/fnsys.2014.0007089585Mesocorticolimbic monoamine correlates of methamphetamine sensitization and motivationKevin D Lominac0Courtney L McKenna1Lisa M Schwartz2Paige N Ruiz3Melissa G Wroten4Bailey W Miller5John J Holloway6Katherine O Travis7Ganesh eRajasekar8Dan eMaliniak9Andrew B Thompson10Lawrence E Urman11Tamara ePhillips12Karen K Szumlinski13University of California, Santa BarbaraUniversity of California, Santa BarbaraUniversity of California, Santa BarbaraUniversity of California, Santa BarbaraUniversity of California, Santa BarbaraUniversity of California, Santa BarbaraUniversity of California, Santa BarbaraUniversity of California, Santa BarbaraUniversity of California, Santa BarbaraUniversity of California, Santa BarbaraUniversity of California, Santa BarbaraUniversity of California, Santa BarbaraOregon Health Sciences UniversityUniversity of California, Santa BarbaraMethamphetamine (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 versus 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.http://journal.frontiersin.org/Journal/10.3389/fnsys.2014.00070/fullDopamineMethamphetamineNucleus AccumbensPrefrontal CortexSerotoninsensitization |
| spellingShingle | 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 eRajasekar Dan eMaliniak Andrew B Thompson Lawrence E Urman Tamara ePhillips Karen K Szumlinski Mesocorticolimbic monoamine correlates of methamphetamine sensitization and motivation Frontiers in Systems Neuroscience Dopamine Methamphetamine Nucleus Accumbens Prefrontal Cortex Serotonin sensitization |
| title | Mesocorticolimbic monoamine correlates of methamphetamine sensitization and motivation |
| title_full | Mesocorticolimbic monoamine correlates of methamphetamine sensitization and motivation |
| title_fullStr | Mesocorticolimbic monoamine correlates of methamphetamine sensitization and motivation |
| title_full_unstemmed | Mesocorticolimbic monoamine correlates of methamphetamine sensitization and motivation |
| title_short | Mesocorticolimbic monoamine correlates of methamphetamine sensitization and motivation |
| title_sort | mesocorticolimbic monoamine correlates of methamphetamine sensitization and motivation |
| topic | Dopamine Methamphetamine Nucleus Accumbens Prefrontal Cortex Serotonin sensitization |
| url | http://journal.frontiersin.org/Journal/10.3389/fnsys.2014.00070/full |
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