Genetic variation in heroin-induced changes in behaviour: effects of B6 strain dose on conditioned reward and locomotor sensitization in 129-B6 hybrid mice.
Substantial interindividual variability exists in the propensity to develop opiate addiction. Genetic variation in opiate reward may contribute to this variability. A large body of evidence indicates genetic variation in mice for several effects of opiate drugs. The present study examined heroin-induced place conditioning and locomotor sensitization in the two strains of mice employed most frequently in the generation of transgenic animals, C57BL/6J (B6) and 129X1/sVJ (129), as well as in groups of B6-129 hybrid mice, differing in their amount of B6 genetic background. Four pairings of 100 microg/kg of heroin elicited robust place conditioning and locomotor sensitization in B6 controls and in N(10) congenic B6-129 hybrid mice. In comparison, the identical treatment produced no locomotor sensitization and induced place aversion in 129 controls. No heroin-induced changes in the behaviour of N(3) congenic B6-129 hybrid mice or F5-8 non-congenic B6-129 hybrid mice were observed. The expression of place conditioning was not facilitated in any group by the administration of a heroin-priming injection prior to testing. These data indicate that genetic variation exists in mice for the rewarding and locomotor-sensitizing effects of heroin and that the capacity of heroin to induce conditioned reward and locomotor sensitization can be modulated in a B6 strain dose-dependent manner in B6-129 hybrid mice. Thus, strain differences in heroin responsiveness should be considered when examining transgenic lines on B6-129 backgrounds for opiate-induced changes in behaviour that may be relevant for addiction.
Szumlinski
K K
KK
Department of Physiology and Neuroscience, and Department of Psychiatry and Behavioral Sciences, Center for Drug and Alcohol Programs, Medical University of South Carolina, Charleston, SC, USA. szumlink@musc.edu
Lominac
K D
KD
Frys
K A
KA
Middaugh
L D
LD
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D003213:Conditioning, Psychological / Q000187:drug effects* / Q000502:physiology; D004777:Environment; D005260:Female; D018628:Gene Dosage; D005824:Genetics, Behavioral; D003932:Heroin / Q000494:pharmacology*; D006824:Hybridization, Genetic / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D012054:Reinforcement, Psychology; D013045:Species Specificity
D003932:Heroin