Differential patterns of opioid and dopamine D1 receptor antagonism on nutritive and non-nutritive sweetener intakes in C57BL/6:129 hybrid mice relative to inbred C57BL/6 and 129 mice

Opioid and dopamine (DA) D1 receptor antagonists differentially reduce nutritive and non-nutritive sweetener intakes in inbred mouse strains. Sucrose intake was more effectively reduced by naltrexone in C57BL/6 (B6) mice relative to 129P3 (129) mice, but more effectively reduced by SCH23390 in 129 mice relative to B6 mice. Opioid and DA D1 antagonists differentially reduced saccharin intakes in B6 mice relative to other strains. Given these differential patterns in sweetener intake in B6 and 129 mice, the present study examined whether systemic naltrexone (0.01-5 mg/kg) and SCH23390 (50-1600 nmol/kg) reduced intakes of 10 % sucrose or 0.2 % saccharin solutions over a 120 min time course in first-generation hybrid mice (B6:129) of B6 and 129 parents and reduced low-nutritive sweetener intakes in 129 mice. Naltrexone (5 mg/kg) significantly reduced 10 % sucrose intake in B6:129 hybrid mice more like that of 129 than B6 mice. In contrast, SCH23390 (400-1600 nmol/kg) reduced 10 % sucrose intake in B6:129 hybrid mice more effectively than that observed in B6 or 129 parental strains. Because 129 mice consumed relatively low amounts of 0.2 % saccharin, they were tested with a more attractive low-nutritive solution containing 0.2 % saccharin and 2 % sucrose. Naltrexone failed to reduce saccharin intake in B6:129 hybrid mice but suppressed saccharin+sucrose intake in 129 mice more like that observed in B6 mice. SCH23390 similarly inhibited saccharin or saccharin+sucrose intakes in hybrid B6:129, 129, and B6 mice with B6 mice more resistant to the lowest SCH23390 dose. Thus, whereas sucrose intake in B6:129 hybrid mice exhibited similar sensitivity to opioid and to a lesser degree DA D1 antagonism to their 129, but not B6 parents, opioid and DA D1 mediation of low- and non-nutritive sweet intake produced unique profiles among B6:129 hybrid and B6 and 129 strains which does not support a simple heritability explanation.