Social isolation at adolescence: a systematic review on behaviour related to cocaine, amphetamine and nicotine use in rats and mice.

Adolescence is known for its high level of risk-taking, and neurobiological alterations during this period may predispose to psychoactive drug initiation and progression into more severe use patterns. Stress is a risk factor for drug consumption, and post-weaning social isolation increases drug self-administration in rodents. This review aimed to provide an overview of the effects of adolescent social isolation on cocaine, amphetamine and nicotine use-related behaviours, highlighting the specific period when animals were submitted to stress and these drugs. We wondered if there was a specific period during adolescence that isolation stress would increase drug use vulnerability. A total of 323 publications from the Scopus, Web of Science and PubMed (Medline) electronic databases were identified using the words "social isolation" and "adolescence" and "drug" or "cocaine" or "amphetamine" or "nicotine", resulting in 24 articles after analyses criteria following the PRISMA statement. The main points raised were social isolation during adolescence increased cocaine self-administration, amphetamine and nicotine locomotor activity. We did not observe a pattern of a specific moment during the adolescent period that could lead to an increased vulnerability to drug use. The precise conditions under which adolescent social stress alters drug use parameters are complex and likely depend on several factors.

Early-life stress affects behavioral and neurochemical parameters differently in male and female juvenile Wistar rats.

Neonatal handling is an early life stressor that leads to behavioral and neurochemical changes in adult rats in a sex-specific manner and possibly affects earlier stages of development. Here, we investigated the effects of neonatal handling (days 1-10 after birth) on juvenile rats focusing on biochemical parameters and olfactory memory after weaning. Male neonatal handled rats performed more crossings on the hole-board task, increased Na+ /K+ -ATPase activity in the olfactory bulb, and decreased acetylcholinesterase activity in the hippocampus versus non-handled males. Female neonatal handled animals increased the number of rearing and nose-pokes on the hole-board task, decreased glutathione peroxidase activity, and total thiol content in the hippocampus versus non-handled females. This study reinforces that early life stress affects behavioral and neurochemical parameters in a sex-specific manner even before the puberty onset.

Comportamento ingestivo de vacas leiteiras em pastagem de azevém alimentadas com diferentes fontes proteicas / Ingestive behavior of dairy cows in annual ryegrass pasture, fed with different proteic sources

Estudou-se o efeito da substituição do farelo de soja da ração por pastejo controlado de trevo-branco (Trifolium repens L.) sobre o comportamento ingestivo de vacas da raça Holandesa em pastejo de azevém (Lolium multiflorum Lam.). Utilizaram-se dois grupos de animais, com média de 20 vacas agrupadas por produção, período de lactação e peso corporal, em delineamento experimental em blocos ao acaso. Um grupo recebeu, diariamente, 3kg de suplemento energético e teve acesso controlado à pastagem de trevo-branco por aproximadamente duas horas e meia (TB); o outro recebeu o mesmo suplemento, adicionado de quantidade de proteína equivalente ao consumo diário no tratamento anterior via trevo, na forma de farelo de soja (FS). Para a avaliação de comportamento, procedeu-se à observação e ao registro do ritmo de atividade dos animais, no período de pastejo em azevém durante dois dias consecutivos, quinzenalmente. Observou-se maior tempo de pastejo em minutos (min), 212,00 versus 194,24min dia-1, e frequência de bocados (bocado), 67,78 versus 64,09 bocado min-1, entre os animais do tratamento FS, em relação ao TB. Não houve diferença no consumo de azevém entre os tratamentos, com valores de 3,65 e 4,11kg vaca-1 dia-1 de matéria seca para TB e FS, respectivamente, o que sugere adequada adaptação dos animais às duas situações estudadas...

The effect of the replacement of soybean meal in the ration with controlled grazing of white clover (Trifolium repens L.) on the ingestive behavior of cows of the holstein breed grazing on annual ryegrass (Lolium multiflorum Lam.) was studied. Two groups of animals with an average of 20 cows grouped by production, lactation period and body weight were used in a randomized block experimental design. One group received 3kg from energy supplement daily and had controlled access to the white clover pasture for approximately 2.5 hours (TB); the other received the same supplement, added of a quantity of protein equivalent to daily intake in previous treatment via white clover, in the form of soybean meal (FS). For behavior assessment the observation and recording of the rhythm of activity of the animals, during the grazing period in ryegrass for two consecutive days, fortnightly was done. The longest grazing time in minutes (min), 212.00 versus 194.24min day-1, and bite frequency (bite), 67.78 versus 64.09 bite min-1, between the animals from treatment FS, when compared to TB was observed. There was no difference in the intake of ryegrass between the treatments, with values of 3.65 and 4.11kg cow-1 day-1 of dry matter for TB and FS, respectively, suggesting adequate adaptation of the animals in the two situations studied...

Neonatal morphine administration leads to changes in hippocampal BDNF levels and antioxidant enzyme activity in the adult life of rats.

It is know that repeated exposure to opiates impairs spatial learning and memory and that the hippocampus has important neuromodulatory effects after drug exposure and withdrawal symptoms. Thus, the aim of this investigation was to assess hippocampal levels of BDNF, oxidative stress markers associated with cell viability, and TNF-α in the short, medium and long term after repeated morphine treatment in early life. Newborn male Wistar rats received subcutaneous injections of morphine (morphine group) or saline (control group), 5 µg in the mid-scapular area, starting on postnatal day 8 (P8), once daily for 7 days, and neurochemical parameters were assessed in the hippocampus on postnatal days 16 (P16), 30 (P30), and 60 (P60). For the first time, we observed that morphine treatment in early life modulates BDNF levels in the medium and long term and also modulates superoxide dismutase activity in the long term. In addition, it was observed effect of treatment and age in TNF-α levels, and no effects in lactate dehydrogenase levels, or cell viability. These findings show that repeated morphine treatment in the neonatal period can lead to long-lasting neurochemical changes in the hippocampus of male rats, and indicate the importance of cellular and intracellular adaptations in the hippocampus after early-life opioid exposure to tolerance, withdrawal and addiction.

Isolation stress exposure and consumption of palatable diet during the prepubertal period leads to cellular changes in the hippocampus.

Social isolation is one of the most potent stressors in the prepubertal period and may influence disease susceptibility or resilience in adulthood. The glucocorticoid response and, consequently, the adaptive response to stress involve important changes in mitochondrial functions and apoptotic signaling. Previous studies have shown that consumption of a palatable diet reduces some stress effects. Therefore, the aim of the present study was to investigate whether isolation stress in early life can lead to cellular alterations in the hippocampus. For this, we evaluated oxidative stress parameters, DNA breakage index, mitochondrial mass and potential, respiratory chain enzyme activities, apoptosis, and necrosis in the hippocampus of juvenile male rats submitted or not to isolation stress during the pre-puberty period. We also verified whether consumption of a palatable diet during this period can modify stress effects. Results show that stress led to an oxidative imbalance, DNA breaks, increased the mitochondrial potential and early apoptosis, and decreased the number of live and necrotic cells. In addition, the palatable diet increased glutathione peroxidase activity, high mitochondrial potential and complex I-III activity in the hippocampus of juvenile rats. The administration of a palatable diet during the isolation period prevented the stress effects that caused the reduction in live cells and increased apoptosis. In conclusion, the stress experienced during the pre-pubertal period induced a hippocampal oxidative imbalance, DNA damage, mitochondrial dysfunction, and increased apoptosis, while consumption of a palatable diet attenuated some of these effects of exposure, such as the reduction in live cells and increased apoptosis, besides favoring an increase in antioxidant enzymes activities.

Composição do leite de vacas Holandesas em pastejo de azevém com a utilização do trevo branco como fonte proteica / Milk composition of Holstein cows grazing ryegrass with the use of white clover as a protein source

Avaliou-se a composição do leite de animais em pastejo de azevém (Lolium multiflorum Lam.) alimentados com trevo branco (Trifolium repens L.) como substituição ao componente proteico da ração (farelo de soja), em porcentagens de proteína, lactose, sólidos totais e contagem de células somáticas. Utilizaram-se dois grupos com oito vacas da raça Holandesa, agrupados por produção, período de lactação e peso corporal, em delineamento em blocos ao acaso. Um grupo recebeu, diariamente, 3kg de suplemento energético subtraído de farelo de soja e teve acesso à pastagem de trevo branco por, aproximadamente, 2,5 horas (TB); o outro recebeu o mesmo suplemento, adicionado de quantidade de proteína equivalente ao consumo diário no tratamento anterior via trevo, na forma de farelo de soja (FS). Foram observadas diferenças significativas para teor de proteína e lactose, sendo os maiores valores encontrados de proteína em TB (3,02%) e de lactose em FS (4,64%). Para as demais variáveis não houve diferença, com valores de 10,40 e 10,39% de sólidos totais e 182,88 e 153,53 (x1000) células somáticas em TB e FS, respectivamente, mostrando que a utilização dessa fonte alternativa de proteína foi eficiente.

Was evaluated the composition of milk from animals grazing annual ryegrass (Lolium multiflorum Lam.) fed with white clover (Trifolium repens L.), as a replacement for the protein component of the ration (soybean meal), in percentages of protein, lactose, total solids and somatic cell counts. Were used two groups with eight Holstein cows, grouped by production, lactation period and body weight, in a randomized block design. One group received 3kg of energetic supplement subtracted of soybean meal daily and had access to the white clover pasture for approximately 2.5 hours (TB); the other received the same supplement, added of a quantity of protein equivalent to daily intake in previous treatment via white clover, in the form of soybean meal (FS). Significant differences were observed for protein and lactose content, with the highest values found for protein on TB (3.02%) and lactose on FS (4.64%). For the other variables there was no difference, with values from 10.40 and 10.39% of total solids and 182.88 and 153.53 (x1000) somatic cells on TB and FS respectively, showing that the use of this alternative source of protein was efficient.

Isolation stress during the prepubertal period in rats induces long-lasting neurochemical changes in the prefrontal cortex.

Social isolation during postnatal development leads to behavioral and neurochemical changes, and a particular susceptibility of the prefrontal cortex to interventions during this period has been suggested. In addition, some studies showed that consumption of a palatable diet reduces some of the stress effects. Therefore, our aim is to investigate the effect of isolation stress in early life on some parameters of oxidative stress and energy metabolism (Na(+),K(+)-ATPase activity, respiratory chain enzymes activities and mitochondrial mass and potential) in prefrontal cortex of juvenile and adult male rats. We also verified if the consumption of a palatable diet during the prepubertal period would reduce stress effects. The results showed that, in juvenile animals, isolation stress increased superoxide dismutase and Complex IV activities and these effects were still observed in the adulthood. An interaction between stress and diet was observed in catalase activity in juveniles, while only the stress effect was detected in adults, reducing catalase activity. Access to a palatable diet increased Na(+),K(+)-ATPase activity in juveniles, an effect that was reversed after removing this diet. On the other hand, isolation stress induced a decreased activity of this enzyme in adulthood. No effects were observed on glutathione peroxidase, total thiols and free radicals production, as well as on mitochondrial mass and potential. In conclusion, isolation stress in the prepubertal period leads to long-lasting changes on antioxidant enzymes and energetic metabolism in the prefrontal cortex of male rats, and a palatable diet was not able to reverse these stress-induced effects.

Consumption of a palatable diet by chronically stressed rats prevents effects on anxiety-like behavior but increases oxidative stress in a sex-specific manner.

It has been proposed that animals subjected to chronic stress show a stress response that can be reduced by the intake of highly palatable foods ("comfort foods"). However, a palatable diet, rich in sugar or fat, can also lead to oxidative damage and neuronal injury. So, the aim of this study is to verify, in male and female rats, the effects of exposure to chronic stress during free access to regular chow and to a highly palatable diet, on exploratory and anxiety-like behavior, on oxidative stress and on DNA breaks in two structures of the nervous system, hippocampus and striatum. The results showed stress- and diet-induced DNA breaks and an imbalance in the activity of antioxidants enzymes, such as CAT, GPx and SOD in the both structures. In addition, we observed that female rats appear to have higher susceptibility to the stress effects evaluated, and that access to a palatable diet was able to counteract some behavioral effects of stress. However, this same diet-induced oxidative stress and increased DNA breaks, especially in males. Replication of these results with larger sample sizes would further reinforce these conclusions.