Verification of a genetic locus for methamphetamine intake and the impact of morphine

Emily C. Eastwood, Amy J. Eshleman, Aaron Janowsky, Tamara Phillips

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Abstract

A quantitative trait locus (QTL) on proximal chromosome (Chr) 10 accounts for > 50% of the genetic variance in methamphetamine (MA) intake in mice selectively bred for high (MAHDR) and low (MALDR) voluntary MA drinking. The µ-opioid receptor (MOP-r) gene, Oprm1, resides at the proximal end of Chr 10, and buprenorphine reduces MA intake in MAHDR mice. However, this drug has only partial agonist effects at MOP-r. We investigated the impact of a full MOP-r agonist, morphine, on MA intake and saccharin intake, measured MOP-r density and affinity in several brain regions of the MA drinking lines and their C57BL/6J (B6) and DBA/2J (D2) progenitor strains, and measured MA intake in two congenic strains of mice to verify the QTL and reduce the QTL interval. Morphine reduced MA intake in the MAHDR line, but also reduced saccharin and total fluid intake. MOP-r density was lower in the medial prefrontal cortex of MAHDR, compared to MALDR, mice, but not in the nucleus accumbens or ventral midbrain; there were no MOP-r affinity differences. No significant differences in MOP-r density or affinity were found between the progenitor strains. Finally, Chr 10 congenic results were consistent with previous data suggesting that Oprm1 is not a quantitative trait gene, but is impacted by the gene network underlying MA intake. Stimulation of opioid pathways by a full agonist can reduce MA intake, but may also non-specifically affect consummatory behavior; thus, a partial agonist may be a better pharmacotherapeutic.

Original languageEnglish (US)
Pages (from-to)1-13
Number of pages13
JournalMammalian Genome
DOIs
StateAccepted/In press - Nov 10 2017

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Genetic Loci
Methamphetamine
Morphine
Chromosomes, Human, Pair 10
Quantitative Trait Loci
Saccharin
Drinking
Consummatory Behavior
Congenic Mice
Buprenorphine
Gene Regulatory Networks
Nucleus Accumbens
Opioid Receptors
Mesencephalon
Prefrontal Cortex
Opioid Analgesics
Genes
Brain

ASJC Scopus subject areas

  • Genetics

Cite this

Verification of a genetic locus for methamphetamine intake and the impact of morphine. / Eastwood, Emily C.; Eshleman, Amy J.; Janowsky, Aaron; Phillips, Tamara.

In: Mammalian Genome, 10.11.2017, p. 1-13.

Research output: Contribution to journalArticle

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