Pre‐ and/or postnatal protein restriction in rats impairs learning and motivation in male offspring

Abstract

Suboptimal developmental environments program offspring to lifelong health complications including affective and cognitive disorders. Little is known about the effects of suboptimal intrauterine environments on associative learning and motivational behavior. We hypothesized that maternal isocaloric low protein diet during pregnancy and lactation would impair offspring associative learning and motivation as measured by operant conditioning and the progressive ratio task, respectively. Control mothers were fed 20% casein (C) and restricted mothers (R) 10% casein to provide four groups: CC, RR, CR, and RC (first letter pregnancy diet and second letter lactation diet), to evaluate effects of maternal diet on male offspring behavior. Impaired learning was observed during fixed ratio-1 operant conditioning in RC offspring that required more sessions to learn vs. the CC offspring (9.4 ± 0.8 and 3.8 ± 0.3 sessions, respectively, p<0.05). Performance in fixed ratio-5 conditioning showed the RR (5.4 ± 1.1), CR (4.0 ± 0.8), and RC (5.0 ± 0.8) offspring required more sessions to reach performance criterion than CC offspring (2.5 ± 0.5, p<0.05). Furthermore, motivational effects during the progressive ratio test revealed less responding in the RR (48.1 ± 17), CR (74.7 ± 8.4), and RC (65.9 ± 11.2) for positive reinforcement vs. the CC offspring (131.5 ± 7.5, p<0.05). These findings demonstrate negative developmental programming effects due to perinatal isocaloric low protein diet on learning and motivation behavior with the nutritional challenge in the prenatal period showing more vulnerability in offspring behavior.

Chronic Maternal Low-Protein Diet in Mice Affects Anxiety, Night-Time Energy Expenditure and Sleep Patterns, but Not Circadian Rhythm in Male Offspring

“…Although our findings were more subtle, a stronger anxiety and/or depressive phenotype in MLP offspring in the CF1 strain of mice [14] and in the more commonly used rat model has been shown [15]. It is known that when comparing behavioral outcomes from different studies, the species and genetic background, as well as the content and exposure timing and length of the MLP diet can have dramatic effects on the severity of the behavioral phenotype of the offspring [2, 11, 13, 15].…”

“…Studies have shown that dietary modifications during gestation can influence neurodevelopment in male [14, 15] and female [14] offspring, manifesting as behavioral changes. Therefore, we carried out a battery of neurobehavioral assays for anxiety, depression, repetitive behaviors, sociability, and learning and memory.…”

“…It is known that when comparing behavioral outcomes from different studies, the species and genetic background, as well as the content and exposure timing and length of the MLP diet can have dramatic effects on the severity of the behavioral phenotype of the offspring [2, 11, 13, 15]. Indeed, a few reports suggest that exposure to MLP during the later stages of gestation and lactation results in an overt behavioral effect, while MLP exposure during the entire gestation period and lactation had variable effects similar to our results [15]. In the current study, virgin female C57BL/6J mice consumed a low-protein diet beginning 4-weeks prior to mating until the end of lactation which is a more relevant model of a chronically malnourished population rather than only gestational MLP.…”

“…Offspring exposed to MLP only during gestation and weaning exhibit signs of anxiety, depression, and impaired learning and memory [14, 15]. In this context, limbic system components such as the hypothalamus, hippocampus, and amygdala, are of particular interest given their potential involvement in MLP-associated neurobehavioral and physiological pathologies [16–19].…”

Maternal protein restriction in the rat during pregnancy and/or lactation alters cognitive and anxiety behaviors of female offspring

“…In regards to motivation for positive reinforcement, prenatally undernourished rats show less appetitive motivation (Miles et al, 2009). We also have reported less motivation in male rats following pre and/or postnatal protein restriction (10% casein) (Reyes‐Castro et al, 2011b).…”