Confirmation of a major QTL influencing oral morphine intake in C57 and DBA mice using reciprocal congenic strains.
C57BL/6 (B6) and DBA/2 (D2) mice exhibit disparate behavior when tested for voluntary morphine intake in a two-bottle choice drinking paradigm with B6 mice consuming 10 times more drug than D2 mice. Previous genetic mapping studies identified a locus, Mop2, on the proximal part of chromosome 10 that explained over half of the genetic variance in this mouse model of opioid self-administration. We constructed a set of reciprocal congenic strains between B6 and D2 mice in which the proximal portion of chromosome 10 has been introgressed from one strain onto the background of the other. We tested mice from this pair of reciprocal strains together with progenitor B6 and D2 mice in a two-bottle choice drinking paradigm with morphine and quinine. The results showed that introgression of chromosome 10 alleles from the B6 strain onto a D2 genetic background increased voluntary morphine intake four-fold compared to progenitor D2 mice. Preference for morphine was also increased significantly in D2.B6-Mop2 mice compared to progenitor D2 mice. Conversely, introgression of chromosome 10 alleles from the D2 strain onto a B6 genetic background decreased morphine intake by half compared to progenitor B6 mice in B6.D2 -Mop2 mice; however, high morphine preference was maintained in this congenic strain most likely due to strong quinine aversion. When quinine was eliminated from the control bottle, morphine preference in B6.D2-Mop2 mice was decreased significantly relative to B6 and D2.B6-Mop2 mice. Overall, these data confirm the existence of a gene(s) on chromosome 10 proximal to D10Mit124 that has a strong influence on the difference in morphine drinking behavior between B6 and D2 mice.
Ferraro
Thomas N
TN
Department of Psychiatry, Center for Neurobiology and Behavior, University of Pennsylvania, Philadelphia, PA 19104-6140, USA. tnf@mail.med.upenn.edu
Golden
Gregory T
GT
Smith
George G
GG
Martin
James F
JF
Schwebel
Candice L
CL
Doyle
Glenn A
GA
Buono
Russell J
RJ
Berrettini
Wade H
WH
D000483:Alleles; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects / Q000235:genetics; D002874:Chromosome Mapping; D004195:Disease Models, Animal; D005260:Female; D005518:Food Preferences / Q000187:drug effects / Q000502:physiology; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D014644:Genetic Variation / Q000235:genetics*; D005838:Genotype; D007178:Inbreeding; D008297:Male; D051379:Mice; D020297:Mice, Congenic; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009020:Morphine / Q000494:pharmacology*; D009021:Morphine Dependence / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D009154:Mutation / Q000235:genetics; D040641:Quantitative Trait Loci / Q000235:genetics*; D011803:Quinine / Q000494:pharmacology; D013045:Species Specificity
D009020:Morphine; D011803:Quinine