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Nutritive (e.g., sucrose) and non-nutritive (e.g., saccharin) sweeteners stimulate intake in inbred mouse strains. BALB/c, SWR and C57BL/6 mice differ in the ability of dopamine (DA) D1 (SCH23390) and opioid (naltrexone) receptor antagonism to alter sucrose intake. Whereas SCH23390 comparably reduced cumulative sucrose intake in all three strains, naltrexone reduced cumulative sucrose intake maximally in C57/BL/6 mice, in intermediate fashion in BALB/c mice, but not in SWR mice. Whereas cumulative saccharin intake was reduced by DA D1 receptor antagonism in BALB/c and SWR mice, naltrexone was more potent in SWR relative to BALB/c mice. The present study first examined whether SCH23390 (50–1600 nmol/kg) and naltrexone (0.01–5 mg/kg) altered saccharin intake in C57BL/6 mice. Given that scopolamine (SCOP), a muscarinic cholinergic receptor antagonist, reduces sweet intake in outbred rats, a second experiment examined whether SCOP (0.1–10 mg/kg) altered 0.2% saccharin and 10% sucrose intakes in BALB/c, SWR and C57BL/6 mice. Cumulative saccharin intake was significantly reduced by SCH23390 (200–1600 nmol/kg; ID40 = 175 nmol/kg) and naltrexone (0.1–5 mg/kg; ID40 > 5 mg/kg) in C57BL/6 mice. Cumulative sucrose intake was significantly reduced following SCOP in C57BL/6 (0.1–10 mg/kg; ID40 = 2.32 mg/kg) and BALB/c (2.5–10 mg/kg; ID40 = 0.52 mg/kg) mice. In contrast, SWR mice (ID40 = 41.61 mg/kg) only displayed transient (15 min) reductions in sucrose intake following SCOP (2.5–10 mg/kg). Cumulative saccharin intake was significantly reduced following SCOP in C57BL/6 and BALB/c mice (0.1–10 mg/kg; ID40 < 0.1 mg/kg). In contrast, SWR mice (ID40 = 2.28 mg/kg) displayed smaller significant reductions in saccharin intake following SCOP (0.1–10 mg/kg). These data indicate that although both nutritive and non-nutritive sweet intakes are governed by muscarinic cholinergic receptor signaling, this process is subject to murine genetic variance with greater sensitivity observed in C57BL/6 and BALB/c relative to SWR inbred mouse strains.Dopamine D1 receptor antagonism reduced saccharin intake in C57BL/6 mice.Opioid receptor antagonism reduced saccharin intake in C57BL/6 mice.Muscarinic antagonism reduced sucrose intake in C57BL/6 and BALB/c mice.Muscarinic antagonism minimally affected sucrose intake in SWR mice.Muscarinic antagonism reduced saccharin intake in all three inbred mouse strains.