Experiment
21 AXB/BXA (A = A/J, B = C57BL/6J) recombinant inbred strains were subject to linkage analysis to detect QTLs associated with cocaine-induced activation of locomotor activity. Animals were administered I.P. injection of 0, 5, 10, or 20 mg/kg cocaine/saline solution and assessed for locomotor activity in an open field box. Progenitor strain A/J exhibits less locomotor activity after administration of cocaine whereas progenitor strain C57BL/6J exhibits a high increase in locomotor activity. Significant linkages mapped to mouse Chromosome 12 at 23 cM (LOD = 5.71 at Iapls2-10), mouse Chromosome 15 at 46.8 cM - 47.9 cM (LOD = 4.72 between Pdgfb and D15Mit105), and mouse Chromosome 17 at 4.1 cM (LOD = 4.25 at D17j2 when controlled for Pdgfb). QTLs are designated Cocia1 (cocaine induced activation), Cocia2, and Cocia3 for loci at Chromosomes 12, 15, and 17, respectively. Possible candidate genes for Cocia1 and Cocia2 are somatostatin receptor 1 (Sstr1) and somatostatin receptor 3 (Sstr3) respectively. Polymorphisms in Smstr3 have been identified in parental strains A/J and C57BL/6J, and polymorphisms have been identified in Sstr1 for C57BL/6J. Interestingly, Cocia2 on mouse Chromosome 15 maps to the same region as cocaine activation QTLs mapped in previous studies (Phillips, J:46922; Jones J: 68421).
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