Genetic variance contributes to dopamine receptor antagonist-induced inhibition of sucrose intake in inbred and outbred mouse strains

Abstract

Preference and intake of sucrose varies across inbred and outbred strains of mice. Pharmacological analyses revealed that the greatest sensitivity to naltrexone-induced inhibition of sucrose (10%) intake was observed in C57BL10/J and C57BL/6J strains, whereas 129P3/J, SWR/J and SJL/J strains displayed far less sensitivity to naltrexone-induced inhibition of sucrose intake. Given that dopamine D1 (SCH23390) and D2 (raclopride) receptor antagonism potently reduce sucrose intake in outbred rat and mouse strains, the present study examined the possibility of genetic variance in the dose-dependent (50–1600 nmol/kg) and time-dependent (5–120 min) effects of these antagonists upon sucrose (10%) intake in the eight inbred (BALB/cJ, C3H/HeJ, C57BL/6J, C57BL/10J, DBA/2J, SJL/J, SWR/J, 129P3/J) and one outbred (CD-1) mouse strains previously tested with naltrexone. SCH23390 significantly reduced sucrose intake across all five doses in 129P3/J and SJL/J mice, across four doses in C57BL/6J and BALB/cJ mice, across three doses in DBA/2J, SWR/J, C3H/HeJ and C57BL/10J mice, but only at the two highest doses in CD-1 mice. SCH23390 was 2–3-fold more potent in inhibiting sucrose intake in 129P3/J and SJL/J mice relative to CD-1 mice. In contrast, only the highest equimolar 1600 nmol/kg dose of raclopride significantly reduced sucrose intake in the BALB/cJ, C3H/HeJ, C57BL/6J, C57BL/10J, DBA/2J, SJL/J and 129P3/J, but not the SWR/J and CD-1 strains. The present and previous data demonstrate specific and differential patterns of genetic variability in inhibition of sucrose intake by dopamine and opioid antagonists, suggesting that distinct neurochemical mechanisms control sucrose intake across different mouse strains.

Different Contributions of Dopamine D1 and D2 Receptor Activity to Alcohol Potentiation of Brain Stimulation Reward in C57BL/6J and DBA/2J Mice

“…Quinpirole elevated but did not lower BSR threshold in DBA mice, suggesting that this strain may have enhanced D2 autoreceptor and/or decreased postsynaptic D2 sensitivity, consistent with previous findings that D2-like receptor binding and mRNA expression are greater in the VTA and substantia nigra pars compacta and lower in the striatum of DBA compared with C57 mice (Ng et al, 1994;Cabib et al, 1998). In both strains, raclopride elevated thresholds and reduced MAX in a dose range similar to previous studies in C57 mice (Riday et al, 2012), and more potently in C57 than DBA mice, which is inconsistent with data on haloperidol-induced catalepsy (Kanes et al, 1993) and suppression of sucrose drinking by raclopride (Dym et al, 2009). Taken together, the differences in responses to quinpirole and raclopride suggest that, regarding reward-related behavior in both C57 and DBA strains, D2 receptors may contribute more than D1 receptors.…”

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

“…The solution was presented in a 10-ml plastic syringe fitted with a stainless steel sipper tube (Dym et al, 2007(Dym et al, , 2009(Dym et al, , 2010. Intakes were measured to the nearest 0.1 ml at 5, 15, 30, 60, 90, and 120 min, and then food and water rations were returned.…”

“…SWR and BALB/c mice, which possess different variants of the Tas1r3 taste receptor gene, thereby making the SWR strain more sweet-sensitive than the BALB/c strain (Reed et al, 2004), also display interesting associations and dissociations in their sensitivity to DA D1 and opioid antagonist effects on intrinsic sugar and fat intake. Whereas SCH produced comparable inhibition of sucrose intake in SWR and BALB/c mice (Dym et al, 2009), it produced potent inhibition of fat (Intralipid) intake in SWR, but no effects in BALB/c mice (Dym et al, 2010). It is unknown whether these effects are due to differences in DA D1 receptor binding between these two strains.…”

“…Conversely, DA D1, but not D2 receptor mediation of fructose intake, has been demonstrated in rats with SCH, but not raclopride suppressing intake (Pritchett and Hajnal, 2011), but opioid receptor mediation of fructose intake is unknown. Therefore, the present study investigated whether DA D1 (SCH) and opioid (NTX) receptor antagonism altered intakes of fructose (8%) and saccharin (0.2%) solutions in these two inbred strains of mice over an identical dose range and time course as was performed for sucrose (Dym et al, 2007(Dym et al, , 2009 and Intralipid (Dym et al, 2010) intake.…”

“…Our laboratory found that marked strain differences occurred in the reduction of sucrose intake following NTX over a wide dose range (0.01-5 mg/kg) in eleven inbred strains (Dym et al, 2007), and following the DA D1 antagonist, SCH23390 (SCH), but not the DA D2 antagonist, raclopride, over a wide dose range (50-1600 nmol/kg) in eight inbred strains (Dym et al, 2009). Correspondingly, marked strain differences occurred in the reduction of fat (Intralipid) following NTX and SCH in 8 inbred strains (Dym et al, 2010).…”