Opioid sensitivity in mice selectively bred to consume or not consume methamphetamine

Emily C. Eastwood, Tamara Phillips

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

There has been little investigation of genetic factors and associated mechanisms that influence risk for development of methamphetamine (MA) dependence. Selectively bred mouse lines that exhibit high (MAHDR) or low (MALDR) levels of MA intake in a two-bottle choice MA drinking (MADR) procedure provide a genetic tool for this purpose. These lines were used to determine whether opioid sensitivity and MA intake are genetically associated, because opioid-mediated pathways influence some effects of MA. Sensitivity to the analgesic effects of the μ-opioid receptor (MOP-r) agonist fentanyl (0.05, 0.1, 0.2, 0.4 mg/kg) was examined using two acute thermal tests (hot plate and tail flick) and one chronic pain test (magnesium sulfate abdominal constriction). Locomotor stimulant responses to fentanyl (0.05, 0.1, 0.2, 0.4 mg/kg) and morphine (10, 20, 30 mg/kg) were also examined. In addition, MADR was measured in the progenitor strains [(C57BL/6J (B6), DBA/2J (D2)] of the F2 population from which the selected lines were generated. The MADR lines did not differ in sensitivity to the analgesic effects of fentanyl; however, MALDR mice exhibited greater locomotor activation than MAHDR mice to both fentanyl and morphine. D2 mice consumed more MA than B6 mice. The line differences for MA consumption and morphine activation recapitulated B6 and D2 strain differences for these two traits, but not strain differences previously found for opioid analgesic responses. These results support a negative genetic correlation between MA consumption and sensitivity to the stimulant effects of opioids and suggest the involvement of MOP-r regulated systems in MA intake.

Original languageEnglish (US)
Pages (from-to)370-379
Number of pages10
JournalAddiction Biology
Volume19
Issue number3
DOIs
StatePublished - 2014

Fingerprint

Methamphetamine
Opioid Analgesics
Fentanyl
Morphine
Drinking
Analgesics
Magnesium Sulfate
Inbred DBA Mouse
Opioid Receptors
Constriction
Chronic Pain
Tail
Hot Temperature

Keywords

  • Amphetamine
  • selective breeding
  • μ-opioid receptor

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Psychiatry and Mental health
  • Pharmacology
  • Medicine(all)

Cite this

Opioid sensitivity in mice selectively bred to consume or not consume methamphetamine. / Eastwood, Emily C.; Phillips, Tamara.

In: Addiction Biology, Vol. 19, No. 3, 2014, p. 370-379.

Research output: Contribution to journalArticle

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