Opioid sensitivity in mice selectively bred to consume or not consume methamphetamine
Article first published online: 12 NOV 2012
Published 2012. This article is a U.S. Government work and is in the public domain in the USA.
Volume 19, Issue 3, pages 370–379, May 2014
How to Cite
Eastwood, E. C. and Phillips, T. J. (2014), Opioid sensitivity in mice selectively bred to consume or not consume methamphetamine. Addiction Biology, 19: 370–379. doi: 10.1111/adb.12003
- Issue published online: 17 APR 2014
- Article first published online: 12 NOV 2012
- Department of Veterans Affairs
- NIH. Grant Number: T32 DA07262
- μ-opioid receptor;
- selective breeding
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.