Linkage analysis was performed on 11 BXD (B=C57BL/6J; D= DBA/2J) recombinant inbred (RI) strains to identify QTLs associated with locomotor activity before and after cocaine treatment. A panel of 2,000 polymorphic markers was used for genotyping. Animalswere assessed for distance traveled in an experimental chamber for 30 minutes. A cocaine solution (10 mg/kg) was then injected intraperitoneally and the animals were assessed for another 30 minutes. Parental strain DBA/2J exhibits increased locomotor activity both before and after cocaine treatment compared to parental strain C57BL/6J. The most significant associations mapped to 26 cM on mouse Chromosome 5 and to 45 cM on mouse Chromosome 9.
The chromosome 5 locus is associated with cocaine-induced locomotor activity and shows linkage to markers Mpmv7 (24 cM), Pmv5 (25 cM), and D5Nds1 (24 cM). This locus reaches the statistical significance level of P<0.001. Association to baseline activity is also observed with a statistical significance level of P<0.05. A potential candidate gene found in this region of chromosome 5 is Drd5 (23 cM).
The chromosome 9 locus is associated with baseline and cocaine-induced locomotor activity at a statistical significance level of P<0.01. This locus shows linkage to markers D9Mit12 (55 cM), Rbp1 (52 cM), Rbp2 (57 cM), D9Ncvs48 (58 cM), and D9Ncvs42 (58 cM). Potential candidate genes mapping near this region are Drd2 (28 cM), Chrna5 (32 cM), Chrna3 (51 cM), Htr1b (46 cM), Cck (71 cM), and Opcml (10 cM). This locus overlaps with a cocaine-induced locomotor activity QTL identified by Tolliver et al, 1994 (J:21289) on mouse Chromosome 9 spanning 38 cM - 57 cM.