Dopamine D1 and opioid receptor antagonist-induced reductions of fructose and saccharin intake in BALB/c and SWR inbred mice

Sugar and fat intake in rodents are mediated in part by brain dopamine (DA) and opioid neurotransmitter systems although important strain differences exist. Thus, whereas sucrose intake of BALB/c and SWR mice was reduced by DA D1 (SCH23390: SCH) receptor antagonism, opioid (naltrexone: NTX) receptor antagonism reduced intake only in BALB/c mice. Both SCH and NTX reduced fat (Intralipid) intake in SWR, but not BALB/c mice. The present study extended this pharmacological analysis to caloric and non-caloric sweeteners by examining whether fructose (8%) or saccharin (0.2%) intakes were differentially suppressed in BALB/c and SWR mice by SCH (50-1600 nmol/kg) or NTX (0.01-5 mg/kg) over a 5- to 120-min time course. SCH significantly reduced fructose (200-1600 nmol/kg) and saccharin (50-1600 nmol/kg) intakes in both strains as did NTX (0.1-5 mg/kg). Antagonist ID₄₀ potencies were < 50 nmol/kg for SCH and 0.9 mg/kg for NTX in inhibiting saccharin intake, and 1234 nmol/kg for SCH and 5 mg/kg for NTX in inhibiting fructose intake in BALB/c mice. For SWR mice, the ID₄₀ potencies were < 50 nmol/kg for SCH and 0.02 mg/kg for NTX in inhibiting saccharin intake, and 298 nmol/kg for SCH and 2.6 mg/kg for NTX in inhibiting fructose intake. Thus, saccharin intake was similarly reduced by SCH and NTX in BALB/c and SWR mice, but greater potencies of opioid (1.9-fold) and DA D1 (4-fold) receptor antagonism of fructose intake were observed in SWR relative to BALB/c mice, indicating strong strain differences.