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. 2007 Apr;86(4):784-96.
doi: 10.1016/j.pbb.2007.03.007. Epub 2007 Mar 28.

Enhanced sensitivity to naltrexone-induced drinking suppression of fluid intake and sucrose consumption in maternally separated rats

Affiliations

Enhanced sensitivity to naltrexone-induced drinking suppression of fluid intake and sucrose consumption in maternally separated rats

Clifford C Michaels et al. Pharmacol Biochem Behav. 2007 Apr.

Abstract

Early-life stress has been identified as a risk factor in the development of a host of disorders, including substance abuse; however the link between early postnatal stress and changes in measures of reward has not been thoroughly researched. The current study had two main objectives: 1) to determine the impact of maternal separation (an animal model of early-life stress) on the consumption of 10% and 2.5% sucrose solutions by Long-Evans rat dams and male and female offspring, and 2) to determine the effect of the opioid antagonist naltrexone (0.1-3.0 mg/kg) on drinking by each of those groups. Dam-pup separations occurred for varying lengths of time during the first two postnatal weeks. In Experiment 1, a two-bottle choice test (sucrose solution vs. water) was administered across five days to both nonhandled (NH) and maternally-separated (MS) offspring as adults and to dams 2-4 weeks post-weaning. In Experiment 2, naltrexone was administered prior to two-bottle choice tests. MS males and the dams of MS litters exhibited increased intake of total fluid and sucrose solutions, whereas results from females were less consistent. Naltrexone elicited a greater decrease in fluid intake and sucrose intake in male MS offspring compared to male NH offspring. These results indicate that early postnatal stress alters both sucrose consumption, a non-drug measure of reward, and apparently the brain opioid systems that mediate naltrexone-induced drinking suppression.

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Figures

Fig. 1
Fig. 1
Dams that underwent separation from their pups (MS) had a higher total fluid intake (top panel) and drank more 10% sucrose solution (middle panel) than did nonhandled dams (NH). However, there was no difference in preference ratio between the two groups (lower panel). Area under the curve (AUC) was also greater for MS dams for total fluid intake (top panel insert) and 10% sucrose intake (middle panel insert) but not for preference ratio (lower panel insert). Mean±S.E.M.; n=12/group. *P<0.05 compared to NH dams.
Fig. 2
Fig. 2
Male MS offspring drank more total fluid (top panels) and sucrose solution (middle panels) at both sucrose concentrations (10% and 2.5%). MS males also had a higher preference ratio than NH males at 10% (lower-left panel) but not at 2.5% sucrose (lower-right panel). Mean±S.E.M.; n=6/group. *P<0.05 compared to NH male offspring.
Fig. 3
Fig. 3
There were no differences in total fluid intake (top panel), 10% sucrose intake (middle panel) or preference ratio (lower panel) when comparing MS females to NH female offspring. Mean±S.E.M.; n=6/group. *P<0.05 compared to MS females.
Fig. 4
Fig. 4
Total fluid intake (top panel), 10% sucrose intake (middle panel), and preference ratio (lower panel) for male non-handled (MNH, white bars), male maternally-separated (MMS, hatched-white), female non-handled (FNH, grey), and female maternally-separated (FMS, hatched-grey) offspring across 5 consecutive days expressed as area under the curve (AUC). Mean±S.E.M.; n=6/group. *P< 0.05 compared to same sex NH, #P< 0.05 compared to females of the same rearing condition.
Fig. 5
Fig. 5
Sex difference between male and female NH and MS offspring. NH females drank more total fluid (top-left panel) and 10% sucrose solution (middle-left panel) than NH males, but did not exhibit a difference in preference ratio (lower-left panel). MS males had a significantly higher preference ratio (lower-right panel) compared to MS females, but did not differ in total fluid intake (top-right panel) or 10% sucrose solution intake (middle-right panel). Mean±S.E.M.; n=6/group. *P< 0.05 compared to females of the same rearing condition.
Fig. 6
Fig. 6
The effects of NTX administration on total fluid intake (top panel), 10% sucrose intake (middle panel) and preference ratio (lower panel) in NH and MS dams. As NTX dose increased, total fluid and 10% sucrose intake decreased in dams of both rearing conditions. A significant dose x rearing interaction was found for preference ratio, with MS dams having a higher ratio at 0.3 mg/kg NTX and NH dams having a higher ratio at 3.0 mg/kg. Mean±S.E.M.; n=6/group. *P< 0.05 compared to NH dams, #P< 0.05 compared to saline control of the same rearing condition.
Fig. 7
Fig. 7
Dose response to NTX administration in male MS and NH offspring. MS males drank more total fluid (top panel), more 10% sucrose solution (middle panel) and had higher sucrose preference ratios (lower panel) than their NH counterparts. Mean±S.E.M.; n=6/group. *P< 0.05 compared to same sex NH offspring, #P< 0.05 compared to saline control of same rearing condition.
Fig. 8
Fig. 8
Dose response to NTX administration in female MS and NH offspring. Results with 10% sucrose solution are on the right, 2.5% sucrose solution left. Females from both groups drank similar amounts of total fluid (top panels) and sucrose solution (middle panels). NH females had higher sucrose preference ratios than MS females at 10% sucrose solution (lower-left panel). Mean±S.E.M.; n=6/group. *P< 0.05 compared to same sex NH offspring, #P< 0.05 compared to saline control of same rearing condition.
Fig. 9
Fig. 9
Sex differences across NTX doses ranging from 0 mg/kg – 3.0 mg/kg. MS and NH females drank more total fluid (top panels) and 10% sucrose (lower panels) compared to males of the same rearing condition. No differences were found for sucrose preference ratio (lower panels). Mean±S.E.M.; n=6/group. *P< 0.05 compared to NH of the same rearing condition, #P< 0.05 compared to saline control of the same rearing condition.

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