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Opioid sensitivity in mice selectively bred to consume or not consume methamphetamine
Author(s) -
Eastwood Emily C.,
Phillips Tamara J.
Publication year - 2014
Publication title -
addiction biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.445
H-Index - 78
eISSN - 1369-1600
pISSN - 1355-6215
DOI - 10.1111/adb.12003
Subject(s) - fentanyl , morphine , stimulant , methamphetamine , opioid , analgesic , agonist , population , μ opioid receptor , pharmacology , medicine , opioid receptor , endocrinology , anesthesia , receptor , environmental health
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 ( B 6), DBA/2J ( D 2)] of the F 2 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. D 2 mice consumed more MA than B 6 mice. The line differences for MA consumption and morphine activation recapitulated B 6 and D 2 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.