Genetic variance contributes to dopamine receptor antagonist-induced inhibition of sucrose intake in inbred and outbred mouse strains.
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 and 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.
Dym
Cheryl T
CT
Department of Psychology, Queens College, The Graduate Center, City University of New York, Flushing, NY 11367, USA.
Pinhas
Alexander
A
Robak
Magdalena
M
Sclafani
Anthony
A
Bodnar
Richard J
RJ
D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D019422:Dietary Sucrose / Q000008:administration & dosage*; D018492:Dopamine Antagonists / Q000494:pharmacology*; D065127:Dopamine D2 Receptor Antagonists; D005518:Food Preferences / Q000187:drug effects* / Q000502:physiology*; D014644:Genetic Variation; D016014:Linear Models; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D020891:Raclopride / Q000494:pharmacology; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D013045:Species Specificity
D001552:Benzazepines; D019422:Dietary Sucrose; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D017447:Receptors, Dopamine D1; D043562:Receptors, G-Protein-Coupled; C534628:SCH 23390; C431926:taste receptors, type 1; D020891:Raclopride