Double-dissociation of D1 and opioid receptor antagonism effects on the acquisition of sucrose-conditioned flavor preferences in BALB/c and SWR mice

Abstract

Sugar appetite is influenced by unlearned attractions to sweet taste and learned responses to sugars' taste and post-ingestive actions. In rats, sugar-conditioned flavor preferences (CFP) are attenuated by dopamine D1 (SCH23390: SCH), but not by opioid (naltrexone: NTX), receptor antagonism. Sucrose-CFP occurs in BALB/c and SWR inbred mice that differ in their suppressive effects of SCH and NTX on sucrose intake. The present study examined whether SCH and NTX altered expression of previously learned sucrose-CFP and acquisition (learning) of sucrose-CFP in these strains. In Experiment 1, food-restricted mice were trained (10 one-bottle sessions) to drink a more-preferred flavored (e.g., cherry) 16% sucrose solution (CS+/Sucrose) on odd-numbered days, and a less-preferred flavored (e.g., grape) 0.05% saccharin solution (CS-/Saccharin) on even-numbered days. Two-bottle tests with the flavors mixed in 0.2% saccharin occurred 30 min following vehicle (Veh), SCH (50-800 nmol/kg) or NTX (1-5mg/kg) assessing preference expression. CS+ preference expression in BALB/c and SWR mice following Veh were significantly reduced by SCH and NTX. In Experiment 2, separate groups of BALB/c and SWR mice received Veh, SCH (50 nmol/kg) or NTX (1mg/kg) injections 30 min prior to daily one-bottle training sessions with the CS+/Sucrose and CS-/Saccharin solutions assessing preference acquisition. Subsequent two-bottle tests with the CS+ vs. CS- solutions were conducted without injections. CS+/Sucrose training intakes were reduced by SCH in both strains and by NTX in BALB/c mice. In the initial two-bottle test, sucrose-CFP acquisition was significantly reduced in BALB NTX (54%), but not in BALB SCH (77%) groups relative to the BALB Veh group (85%). In contrast, sucrose-CFP acquisition was significantly reduced in SWR SCH (61%), but not in SWR NTX (83%) groups relative to the SWR Veh group (86%). DA D1 and opioid receptor signaling modulate acquisition and/or expression of sucrose-CFP in mice with significant strain differences observed.

Figure 1

(Expression Procedure). Intakes (mean +SEM, g/1 h) of CS+ and CS− solutions in two-bottle tests in BALB (upper panel) and SWR (lower panel) inbred mice receiving systemic injections of the DA D1-like antagonist, SCH23390 at doses of 0, 50, 200 and 800 nmol/kg 30 min prior to testing. Significant differences in this and the next figure are denoted between CS+ and CS− intake within an injection condition (*) and between CS+ intake following a drug dose relative to the vehicle treatment (+). The percentages of CS+ intake over total intake are denoted above each pair of values with significant differences relative to vehicle treatment (*) noted.

Figure 2

(Expression Procedure). Intakes (mean +SEM, g/1 h) of CS+ and CS− solutions in two-bottle tests in BALB (upper panel) and SWR (lower panel) inbred mice receiving systemic injections of the general opioid antagonist, naltrexone at doses of 0, 1 and 5 mgl/kg 30 min prior to testing.

Figure 3

(Acquisition Procedure). Upper Panel: Training intakes (mean +SEM, g/1 h) of CS+/Sucrose and CS−/Saccharin solutions in BALB mice pretreated 30 min earlier with vehicle (Veh), SCH23390 at a dose of 50 nmol/kg (SCH) or naltrexone at a dose of 1 mg/kg (NTX). Significant differences in this and the next figure are denoted between CS+/Sucrose and CS−/Saccharin intakes within each group (*) as are significant differences in CS+/Sucrose or CS+/Saccharin intakes following SCH or NTX relative to corresponding Veh (+). Lower Panel: Testing intakes (mean +SEM, g/1 h) of CS+ and CS− solutions during two-bottle Tests 1 and 2 in BALB mice receiving Veh, SCH or NTX during training. Numbers atop bars represent the mean percent intakes of CS+ (%CS+). Significant differences in this and the next figure are denoted between CS+ and CS− intake and for %CS+ intake within each test (*).

Figure 4

(Acquisition Procedure). Upper Panel: Training intakes (mean +SEM, g/1 h) of CS+/Sucrose and CS−/Saccharin solutions in SWR mice pretreated 30 min earlier with vehicle (Veh), SCH23390 at a dose of 50 nmol/kg (SCH) or naltrexone at a dose of 1 mg/kg (NTX). Lower Panel: Testing intakes (mean +SEM, g/60 min) of CS+ and CS− solutions during two-bottle Tests 1 and 2 in SWR mice receiving Veh, SCH or NTX during training. Numbers atop bars represent the mean percent intakes of CS+ (%CS+). The Y-axis has been modified to accommodate the increased intake of this strain in this paradigm.