title: 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-hour 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, dose-dependently 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.
authors.affiliation: Department of Psychology, Queens College, The Graduate Center, City University of New York, Flushing, NY 11367, USA.
authors.forename: Cheryl T
authors.initials: CT
authors.lastname: Dym
authors.forename: Veronica S
authors.initials: VS
authors.lastname: Bae
authors.forename: Tamar
authors.initials: T
authors.lastname: Kraft
authors.forename: Yakov
authors.initials: Y
authors.lastname: Yakubov
authors.forename: Amanda
authors.initials: A
authors.lastname: Winn
authors.forename: Anthony
authors.initials: A
authors.lastname: Sclafani
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Bodnar
mesh_terms: D000818:Animals; D021461:Animals, Outbred Strains; D001552:Benzazepines / Q000008:administration & dosage / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005217:Fat Emulsions, Intravenous / Q000008:administration & dosage*; D005247:Feeding Behavior / Q000187:drug effects* / Q000502:physiology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009271:Naltrexone / Q000008:administration & dosage / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011957:Receptors, Opioid / Q000378:metabolism; D013045:Species Specificity; D013997:Time Factors
chemical_list: D001552:Benzazepines; D018492:Dopamine Antagonists; D005217:Fat Emulsions, Intravenous; D009292:Narcotic Antagonists; D017447:Receptors, Dopamine D1; D011957:Receptors, Opioid; C534628:SCH 23390; D009271:Naltrexone