Sugar Overconsumption during Adolescence Selectively Alters Motivation and Reward Function in Adult Rats

International audienceBACKGROUND:There has been a dramatic escalation in sugar intake in the last few decades, most strikingly observed in the adolescent population. Sugar overconsumption has been associated with several adverse health consequences, including obesity and diabetes. Very little is known, however, about the impact of sugar overconsumption on mental health in general, and on reward-related behavioral disorders in particular. This study examined in rats the effects of unlimited access to sucrose during adolescence on the motivation for natural and pharmacological rewards in adulthood.METHODOLOGY/PRINCIPAL FINDINGS:Adolescent rats had free access to 5% sucrose or water from postnatal day 30 to 46. The control group had access to water only. In adulthood, rats were tested for self-administration of saccharin (sweet), maltodextrin (non-sweet), and cocaine (a potent drug of abuse) using fixed- and progressive-ratio schedules, and a concentration-response curve for each substance. Adult rats, exposed or not exposed to sucrose, were tested for saccharin self-administration later in life to verify the specificity of adolescence for the sugar effects. Sugar overconsumption during adolescence, but not during adulthood, reduced the subsequent motivation for saccharin and maltodextrin, but not cocaine. This selective decrease in motivation is more likely due to changes in brain reward processing than changes in gustatory perception.CONCLUSIONS/SIGNIFICANCE:Sugar overconsumption induces a developmental stage-specific chronic depression in reward processing that may contribute to an increase in the vulnerability to reward-related psychiatric disorders

Estradiol, insulin-like growth factor-I and brain aging

The decrease in some hormones with aging, such as insulin-like growth factor-I (IGF-I) and estradiol, may have a negative impact on brain function. Estradiol and IGF-I may antagonize the damaging effects of adrenal steroids and other causes of brain deterioration. The signaling of estradiol and IGF-I interact to promote neuroprotection. Estrogen receptor α, in an estrogen-dependent process, can physically interact with IGF-I receptor and with the downstream signaling molecules of the phosphotidylinositol 3-kinase (PI3K)/Akt/glycogen synthase kinase 3 (GSK3) pathway. Estradiol and IGF-I have a synergistic effect on the activation of Akt, which in turn decreases the activity of GSK3. This may be one of the mechanisms used by estradiol to promote neuronal survival, since the inhibition of GSK3 is associated to the activation of surviving signaling pathways in neurons. Furthermore, estradiol may control Tau phosphorylation by modulating the interactions of estrogen receptor α with GSK3 and β-catenin, another molecule involved in the regulation of neuronal survival and the reorganization of the cytoskeleton. All these actions may be involved in the neuroprotective effects of the hormone. Possible aging-associated changes in the expression or activity of these signaling molecules may affect estradiol neuroprotective effects. Therefore, it is important to determine whether aging affects the signaling of estradiol and IGF-I in the brain. © 2007 Elsevier Ltd. All rights reserved.Peer Reviewe

The effect of restraint stress on paradoxical sleep is influenced by the circadian cycle

International audienceIt is well known that the physiological impact imposed by events or behaviors displayed during the waking period determines the way organisms sleep. Among the situations known to affect sleep both in its duration and quality, stress has been widely studied and it is now admitted that its effects on sleep architecture depend on several factors specific to the stressor or the individual itself. Although numerous reports have highlighted the prominent role of the circadian cycle in the physiological, endocrine and behavioral consequences of restraint stress, a possible circadian influence in the effects of stress on the sleep-wake cycle has never been studied. Thus the present study was designed to compare the effects on sleep of a 1 h-lasting restraint stress applied at light onset to those observed after the same stressor was applied at light offset. We report that in both conditions stress induced a marked paradoxical sleep increase, whereas wakefulness displayed a moderate decrease and slow wave sleep a moderate augmentation. Although the effects of stress at lights on were of similar magnitude than those of stress at lights off, important differences in the sleep rebound latencies were observed: whatever the time of day the stress was applied, its effects on sleep always occurred during the dark period. This result thus shows that restraint stress could be efficiently used to study the interaction between the circadian and homeostatic components of sleep regulation

Insulin-like growth factor 1 reduces age-related disorders induced by prenatal stress in female rats

Stress during the prenatal period can induce permanent abnormalities in adult life such as increased anxiety-like behavior and hyperactivity of hypothalamo-pituitary-adrenal (HPA) axis system. The present study was designed to investigate whether prenatal stress could induce spatial learning impairment in aged female rats. Furthermore, since it has been recently reported that insulin-like growth factor 1 (IGF-1) attenuates spatial learning deficits in aged rats and promotes neurogenesis in the hippocampus, we assessed the impact of a chronic infusion of IGF-1 on age-related disorders. Our results show that females stressed during prenatal life exhibit learning impairments in the water maze task. Chronic IGF-1 treatment restores their spatial abilities, reduces their HPA axis dysfunction and increases plasma estradiol levels. Parallel to these effects, chronic IGF-1 up-regulates neural proliferation in the dentate gyrus of the hippocampus. These findings support the hypothesis of an early programming of the vulnerability to some neurological diseases during senescence and reinforce the potential therapeutic interest of IGF-1 during brain aging. © 2005 Elsevier Inc. All rights reserved.Peer Reviewe

Early motherhood in rats is associated with a modification of hippocampal function

The transition to motherhood results in a number of hormonal, neurological and behavioral changes necessary to ensure offspring survival. However, little attention has been paid to changes not directly linked to reproductive function in the early mother. In this study, we demonstrate that spatial performances during the learning phase were impaired after the delivery in rats, while spatial retention ability was improved 2 weeks later. In addition, we also report that early motherhood reduced the cell proliferation in the dentate gyrus of the hippocampus without inducing a decrease in the newborn cells 2 weeks later. The decrease of estradiol levels and high levels of glucocorticoids after delivery could in part explain the changes in the hippocampal function. In summary, our findings suggest that early postpartum period is associated with a modification of hippocampal function. This may reflect a homeostatic form of hippocampal plasticity in response to the onset of the maternal experience. © 2007 Elsevier Ltd. All rights reserved.Peer Reviewe

Neurosteroids: Deficient cognitive performance in aged rats depends on low pregnenolone sulfate levels in the hippocampus

Pregnenolone sulfate (PREG S) is synthesized in the nervous system and is a major neurosteroid in the rat brain. Its concentrations were measured in the hippocampus and other brain areas of single adult and aged (22–24 month-old) male Sprague–Dawley rats. Significantly lower levels were found in aged rats, although the values were widely scattered and reached, in about half the animals, the same range as those of young ones. The spatial memory performances of aged rats were investigated in two different spatial memory tasks, the Morris water maze and Y-maze. Performances in both tests were significantly correlated and, accompanied by appropriate controls, likely evaluated genuine memory function. Importantly, individual hippocampal PREG S and distance to reach the platform in the water maze were linked by a significant correlation, i.e., those rats with lower memory deficit had the highest PREG S levels, whereas no relationship was found with the PREG S content in other brain areas (amygdala, prefrontal cortex, parietal cortex, striatum). Moreover, the memory deficit of cognitively impaired aged rats was transiently corrected after either intraperitoneal or bilateral intrahippocampal injection of PREG S. PREG S is both a γ-aminobutyric acid antagonist and a positive allosteric modulator at the N-methyl-d-aspartate receptor, and may reinforce neurotransmitter system(s) that decline with age. Indeed, intracerebroventricular injection of PREG S was shown to stimulate acetylcholine release in the adult rat hippocampus. In conclusion, it is proposed that the hippocampal content of PREG S plays a physiological role in preserving and/or enhancing cognitive abilities in old animals, possibly via an interaction with central cholinergic systems. Thus, neurosteroids should be further studied in the context of prevention and/or treatment of age-related memory disorders