Genetic variance contributes to dopamine and opioid receptor antagonist-induced inhibition of intralipid (fat) intake in inbred and outbred mouse strains

Abstract

Preference for and intake of solid and emulsified fat (Intralipid) solutions vary across different mouse strains. Fat intake in rodents is inhibited by dopamine and opioid receptor antagonists, but any variation in these responses as a function of genetic background is unknown. Therefore, the present study compared the ability of dopamine D1-like (SCH23390) and general opioid (naltrexone) receptor antagonism to alter intake of fat emulsions (Intralipid) in mice. Two-h intakes of 5% Intralipid were measured (5-120 min) in seven inbred (BALB/c, C57BL/6, C57BL/10, DBA/2, SJL, SWR, 129P3) and one outbred (CD-1) mouse strains following treatment with vehicle, SCH23390 (50-1600 nmol/kg, ip) and naltrexone (0.001-5 mg/kg, sc). SCH23390 significantly, dosedependently and differentially reduced Intralipid intake at all five (DBA/2, SWR, CD-1), four (SJL, C57BL/6), three (129P3) and one (C57BL/10) of the doses tested, but failed to affect Intralipid intake in BALB/c mice. Naltrexone significantly, dose-dependently and differentially reduced Intralipid intake at all four (DBA/2), three (SWR, SJL), two (CD-1, C57BL/10) and one (C57BL/6, 129P3) of the doses tested, and also failed to affect Intralipid intake in BALB/cJ mice. SCH23390 and naltrexone were respectively 13.3-fold and 9.3-fold more potent in inhibiting Intralipid intake in the most sensitive (DBA/2) relative to the least sensitive (BALB/c) mouse strains. A strong positive relationship (r=0.91) was observed for the abilities of SCH23390 and naltrexone to inhibit Intralipid intake across strains. These findings indicate that dopaminergic and opioid signaling mechanisms differentially control Intralipid intake across different mouse strains, suggesting important genetic and pharmacological interactions in the short-term control of rewarding and post-ingestive consequences of fat intake.

Mechanisms Involved in Guiding the Preference for Fat Emulsion Differ Depending on the Concentration

“…Furthermore, we have also demonstrated that fat ingestion can activate pro-opiomelanocortin (POMC) neurons in the hypothalamus, which synthesize beta-endorphin (5). Many reports have suggested that administration of opioid receptor antagonists can attenuate fat preference, an observation that is consistent with our findings (4,(6)(7)(8).…”

“…Furthermore, we have also demonstrated that fat ingestion can activate pro-opiomelanocortin (POMC) neurons in the hypothalamus, which synthesize beta-endorphin (5). Many reports have suggested that administration of opioid receptor antagonists can attenuate fat preference, an observation that is consistent with our findings (4,(6)(7)(8).A significant amount of experimental evidence implicates the opioid system in the reward and reinforcement of drug addiction. We previously demonstrated that, similar to drug administration, fat ingestion can serve as a reinforcer by inducing place preference or strong lever-pressing behavior in mice (we define these as "reinforcing effects") (9, 10).…”

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

“…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). In addition to the intrinsic palatability of sugars, sucrose and fructose elicit conditioned flavor preferences (CFP) that are also subject to marked differences across 8 inbred strains (Pinhas et al, 2012).…”

“…Whereas NTX moderately inhibited sucrose intake in BALB/c mice, it was ineffective in SWR mice (Dym et al, 2007). Conversely, NTX suppressed Intralipid intake in SWR, but not BALB/c mice (Dym et al, 2010). Although no studies have examined whether these two strains differ in opioid receptor binding, SWR mice display attenuated opioid-mediated responses to rewards as evaluated in morphine self-administration (Belknap et al, 1993) and conditioned place preference (Gieryk et al, 2010;Solecki et al, 2009).…”

“…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.…”