Rats were trained in a step-down inhibitory avoidance task and retrieval was measured during a te... more Rats were trained in a step-down inhibitory avoidance task and retrieval was measured during a test session conducted 24 h after training. The ip administration of a low dose of gamma-endorphin (0.2 micrograms/kg) immediately after training reduced retrieval time from 40.6 to 13.5 s (N = 15). Higher doses of gamma-endorphin given 5 min before testing (1.0 micrograms/kg) or immediately after training (5 micrograms/kg) enhanced retrieval time from 38.6 to 300 s (N = 15) and from 40.6 to 104.4 s (N = 15). All of these effects were blocked by pretreatment with naloxone (0.4 mg/kg). Alpha-endorphin (0.2, 1.0 or 5.0 micrograms/kg) administered either after training or before testing had no effect on retrieval. Since at least the amnestic effect of gamma-endorphin is similar to that of beta-endorphin, and gamma-endorphin is a possible metabolite of beta-endorphin by limited proteolysis of the carboxyl-terminal amino acid, it is suggested that at least some effects of beta-endorphin on memory may be mediated by its proteolysis product, gamma-endorphin.
Exposure to stressors in early postnatal life induces long-lasting modifications in brain functio... more Exposure to stressors in early postnatal life induces long-lasting modifications in brain function. This plasticity, an essential characteristic of the brain that enables adaptation to the environment, may also induce impairments in some psychophysiological functions, including learning and memory. Early life stress (ELS) has long-term effects on the hypothalamic-pituitary-adrenal axis response to stressors, and has been reported to lead to neuroinflammation, altered levels of neurotrophic factors, modifications in neurogenesis and synaptic plasticity, with changes in neurotransmitter systems and network functioning. In this review, we focus on early postnatal stress in animal models and their effects on learning and memory. Many studies have reported ELSinduced impairments in different types of memories, including spatial memory, fear memory, recognition (both for objects and social) memory, working memory and reversal learning. Studies are not always in agreement, however, no effects, or sometimes facilitation, being reported, depending on the nature and intensity of the early intervention, as well as the age when the outcome was evaluated and the sex of the animals. When considering processes occurring after consolidation, related with memory maintenance/persistence or transformation, there are a very reduced number of reports. Future studies addressing the mechanisms underlying memory changes for ELS should shed some light on the understanding of the different effects induced by stressors of different types and intensities on cognitive functions. This article is part of a Special Issue entitled: In memory of Ivan Izquierdo South American pioneer of the Neuroscience of Memory Temporal dynamics and molecular mechanisms.
British journal of medicine and medical research, Jan 10, 2014
Aim: the aim of this study was to induce obesity in rats using the neonatal overfeeding protocol ... more Aim: the aim of this study was to induce obesity in rats using the neonatal overfeeding protocol and evaluate in adult male animals standard chow intake, sweet food intake, the preference between sweet food and standard chow, locomotor activity and anxiety-like behavior. Methodology: The neonatal overfeeding protocol consisted of reducing the litter size to 4 animals (small litters = SL) compared to 8 animals in normal litters (NL). In these experiments we used 55 offspring from 18 litters. Results: obesity was successfully induced as observed by increased body weight and Original Research Article British Journal of Medicine & Medical Research, 4(4): 957-968, 2014 958 depots of abdominal fat in SL animals compared to NL; [F(1, 53)=15.018; P<.001] for body weight and [t(48.06)=2.186 P=.03] for abdominal fat.No difference between groups was found in standard chow [t (16)=1.843 P=.08] and sweet food intake [t(53)=0.453 P=.65], however in the test that evaluated the preference between both foods SL animals consumed more sweet food than NL [t(48) =2.481 P=.02]. Additionally, there was no difference between groups regarding locomotor activity [t(52)=0.073 P=.94] but SL animals showed reduced anxiety-like behavior compared to NL [t(39.36)=2.205 P=.03]. Conclusion: this study supports the use of neonatal overfeeding protocol as a model of early obesity and showed for the first time the increased preference for sweet food in adult neonatal overfed animals.
Postnatal overfeeding is a well-known model of early-life induced obesity and glucose intolerance... more Postnatal overfeeding is a well-known model of early-life induced obesity and glucose intolerance in rats. However, little is known about its impact on insulin signaling in specific brain regions such as the mesocorticolimbic system, and its putative effects on dopamine-related hedonic food intake in adulthood. For this study, rat litters were standardized to 4 (small litter - SL) or 8 pups (control - NL) at postnatal day 1. Weaning was at day 21, and all tests were conducted after day 60 of life in male rats. In Experiment 1, we demonstrated that the SL animals were heavier than the NL at all time points and had decreased AKT/pAKT ratio in the Ventral Tegmental Area (VTA), without differences in the skeletal muscle insulin signaling in response to insulin injection. In Experiment 2, the standard rat chow intake was addressed using an automated system (BioDAQ, Research Diets(®)), and showed no differences between the groups. On the other hand, the SL animals ingested more sweet food in response to the 1min tail-pinch challenge and did not develop conditioned place preference to sweet food. In Experiment 3 we showed that the SL rats had increased VTA TH content but had no difference in this protein in response to a sweet food challenge, as the NL had. The SL rats also showed decreased levels of dopamine D2 receptors in the nucleus accumbens. Here we showed that early postnatal overfeeding was linked to an altered functioning of the mesolimbic dopamine pathway, which was associated with altered insulin signaling in the VTA, suggesting increased sensitivity, and expression of important proteins of the dopaminergic system.
Rats were trained in a step-down inhibitory avoidance task and retrieval was measured during a te... more Rats were trained in a step-down inhibitory avoidance task and retrieval was measured during a test session conducted 24 h after training. The ip administration of a low dose of gamma-endorphin (0.2 micrograms/kg) immediately after training reduced retrieval time from 40.6 to 13.5 s (N = 15). Higher doses of gamma-endorphin given 5 min before testing (1.0 micrograms/kg) or immediately after training (5 micrograms/kg) enhanced retrieval time from 38.6 to 300 s (N = 15) and from 40.6 to 104.4 s (N = 15). All of these effects were blocked by pretreatment with naloxone (0.4 mg/kg). Alpha-endorphin (0.2, 1.0 or 5.0 micrograms/kg) administered either after training or before testing had no effect on retrieval. Since at least the amnestic effect of gamma-endorphin is similar to that of beta-endorphin, and gamma-endorphin is a possible metabolite of beta-endorphin by limited proteolysis of the carboxyl-terminal amino acid, it is suggested that at least some effects of beta-endorphin on memory may be mediated by its proteolysis product, gamma-endorphin.
Exposure to stressors in early postnatal life induces long-lasting modifications in brain functio... more Exposure to stressors in early postnatal life induces long-lasting modifications in brain function. This plasticity, an essential characteristic of the brain that enables adaptation to the environment, may also induce impairments in some psychophysiological functions, including learning and memory. Early life stress (ELS) has long-term effects on the hypothalamic-pituitary-adrenal axis response to stressors, and has been reported to lead to neuroinflammation, altered levels of neurotrophic factors, modifications in neurogenesis and synaptic plasticity, with changes in neurotransmitter systems and network functioning. In this review, we focus on early postnatal stress in animal models and their effects on learning and memory. Many studies have reported ELSinduced impairments in different types of memories, including spatial memory, fear memory, recognition (both for objects and social) memory, working memory and reversal learning. Studies are not always in agreement, however, no effects, or sometimes facilitation, being reported, depending on the nature and intensity of the early intervention, as well as the age when the outcome was evaluated and the sex of the animals. When considering processes occurring after consolidation, related with memory maintenance/persistence or transformation, there are a very reduced number of reports. Future studies addressing the mechanisms underlying memory changes for ELS should shed some light on the understanding of the different effects induced by stressors of different types and intensities on cognitive functions. This article is part of a Special Issue entitled: In memory of Ivan Izquierdo South American pioneer of the Neuroscience of Memory Temporal dynamics and molecular mechanisms.
British journal of medicine and medical research, Jan 10, 2014
Aim: the aim of this study was to induce obesity in rats using the neonatal overfeeding protocol ... more Aim: the aim of this study was to induce obesity in rats using the neonatal overfeeding protocol and evaluate in adult male animals standard chow intake, sweet food intake, the preference between sweet food and standard chow, locomotor activity and anxiety-like behavior. Methodology: The neonatal overfeeding protocol consisted of reducing the litter size to 4 animals (small litters = SL) compared to 8 animals in normal litters (NL). In these experiments we used 55 offspring from 18 litters. Results: obesity was successfully induced as observed by increased body weight and Original Research Article British Journal of Medicine & Medical Research, 4(4): 957-968, 2014 958 depots of abdominal fat in SL animals compared to NL; [F(1, 53)=15.018; P<.001] for body weight and [t(48.06)=2.186 P=.03] for abdominal fat.No difference between groups was found in standard chow [t (16)=1.843 P=.08] and sweet food intake [t(53)=0.453 P=.65], however in the test that evaluated the preference between both foods SL animals consumed more sweet food than NL [t(48) =2.481 P=.02]. Additionally, there was no difference between groups regarding locomotor activity [t(52)=0.073 P=.94] but SL animals showed reduced anxiety-like behavior compared to NL [t(39.36)=2.205 P=.03]. Conclusion: this study supports the use of neonatal overfeeding protocol as a model of early obesity and showed for the first time the increased preference for sweet food in adult neonatal overfed animals.
Postnatal overfeeding is a well-known model of early-life induced obesity and glucose intolerance... more Postnatal overfeeding is a well-known model of early-life induced obesity and glucose intolerance in rats. However, little is known about its impact on insulin signaling in specific brain regions such as the mesocorticolimbic system, and its putative effects on dopamine-related hedonic food intake in adulthood. For this study, rat litters were standardized to 4 (small litter - SL) or 8 pups (control - NL) at postnatal day 1. Weaning was at day 21, and all tests were conducted after day 60 of life in male rats. In Experiment 1, we demonstrated that the SL animals were heavier than the NL at all time points and had decreased AKT/pAKT ratio in the Ventral Tegmental Area (VTA), without differences in the skeletal muscle insulin signaling in response to insulin injection. In Experiment 2, the standard rat chow intake was addressed using an automated system (BioDAQ, Research Diets(®)), and showed no differences between the groups. On the other hand, the SL animals ingested more sweet food in response to the 1min tail-pinch challenge and did not develop conditioned place preference to sweet food. In Experiment 3 we showed that the SL rats had increased VTA TH content but had no difference in this protein in response to a sweet food challenge, as the NL had. The SL rats also showed decreased levels of dopamine D2 receptors in the nucleus accumbens. Here we showed that early postnatal overfeeding was linked to an altered functioning of the mesolimbic dopamine pathway, which was associated with altered insulin signaling in the VTA, suggesting increased sensitivity, and expression of important proteins of the dopaminergic system.
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Papers by Carla Dalmaz