Controversies about the enhanced vulnerability of the adolescent brain to develop addiction.

Adolescence, defined as a transition phase toward autonomy and independence, is a natural time of learning and adjustment, particularly in the setting of long-term goals and personal aspirations. It also is a period of heightened sensation seeking, including risk taking and reckless behaviors, which is a major cause of morbidity and mortality among teenagers. Recent observations suggest that a relative immaturity in frontal cortical neural systems may underlie the adolescent propensity for uninhibited risk taking and hazardous behaviors. However, converging preclinical and clinical studies do not support a simple model of frontal cortical immaturity, and there is substantial evidence that adolescents engage in dangerous activities, including drug abuse, despite knowing and understanding the risks involved. Therefore, a current consensus considers that much brain development during adolescence occurs in brain regions and systems that are critically involved in the perception and evaluation of risk and reward, leading to important changes in social and affective processing. Hence, rather than naive, immature and vulnerable, the adolescent brain, particularly the prefrontal cortex, should be considered as prewired for expecting novel experiences. In this perspective, thrill seeking may not represent a danger but rather a window of opportunities permitting the development of cognitive control through multiple experiences. However, if the maturation of brain systems implicated in self-regulation is contextually dependent, it is important to understand which experiences matter most. In particular, it is essential to unveil the underpinning mechanisms by which recurrent adverse episodes of stress or unrestricted access to drugs can shape the adolescent brain and potentially trigger life-long maladaptive responses.

The brain in the jar : troubling the truths of discourses of adolescent brain development

Ideas about adolescent brains and their development increasingly function as powerful truths in making sense of young people. And it is the knowledge practices of the neurosciences and evolutionary and developmental psychology that are deemed capable of producing what we have come to understand as the evidence on which policy, interventions and education should be built. In effect these discourses reduce young people to little more than a brain in a jar. The paper examines how the evidence about adolescent brains - their volume, and the functioning and activity of different regions - from neuroscience and evolutionary and developmental psychology works as truth. What knowledge practices are used to produce this evidence, or are deemed capable of producing this evidence? What truth claims are able to attach to this evidence? What makes it true and why is it imagined as evidence of something that is true in policy, public and other research settings that are often far removed from where it was produced? I argue that the discourses of adolescent brain development disembody, reduce and simplify the complexities of these figures we know as adolescents. In effect they render the adolescent as a brain in a jar.

Variation in pediatric traumatic brain injury outcomes in the United States.

OBJECTIVE: To ascertain the degree of variation, by state of hospitalization, in outcomes associated with traumatic brain injury (TBI) in a pediatric population. DESIGN: A retrospective cohort study of pediatric patients admitted to a hospital with a TBI. SETTING: Hospitals from states in the United States that voluntarily participate in the Agency for Healthcare Research and Quality's Healthcare Cost and Utilization Project. PARTICIPANTS: Pediatric (age ≤ 19 y) patients hospitalized for TBI (N=71,476) in the United States during 2001, 2004, 2007, and 2010. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Primary outcome was proportion of patients discharged to rehabilitation after an acute care hospitalization among alive discharges. The secondary outcome was inpatient mortality. RESULTS: The relative risk of discharge to inpatient rehabilitation varied by as much as 3-fold among the states, and the relative risk of inpatient mortality varied by as much as nearly 2-fold. In the United States, approximately 1981 patients could be discharged to inpatient rehabilitation care if the observed variation in outcomes was eliminated. CONCLUSIONS: There was significant variation between states in both rehabilitation discharge and inpatient mortality after adjusting for variables known to affect each outcome. Future efforts should be focused on identifying the cause of this state-to-state variation, its relationship to patient outcome, and standardizing treatment across the United States.

Patterns of exposure to infectious diseases and social contacts in early life and risk of brain tumours in children and adolescents: an International Case-Control Study (CEFALO)

BACKGROUND Infectious diseases and social contacts in early life have been proposed to modulate brain tumour risk during late childhood and adolescence. METHODS CEFALO is an interview-based case-control study in Denmark, Norway, Sweden and Switzerland, including children and adolescents aged 7-19 years with primary intracranial brain tumours diagnosed between 2004 and 2008 and matched population controls. RESULTS The study included 352 cases (participation rate: 83%) and 646 controls (71%). There was no association with various measures of social contacts: daycare attendance, number of childhours at daycare, attending baby groups, birth order or living with other children. Cases of glioma and embryonal tumours had more frequent sick days with infections in the first 6 years of life compared with controls. In 7-19 year olds with 4+ monthly sick day, the respective odds ratios were 2.93 (95% confidence interval: 1.57-5.50) and 4.21 (95% confidence interval: 1.24-14.30). INTERPRETATION There was little support for the hypothesis that social contacts influence childhood and adolescent brain tumour risk. The association between reported sick days due to infections and risk of glioma and embryonal tumour may reflect involvement of immune functions, recall bias or inverse causality and deserve further attention.

HPA Axis Activation by Ethanol Dependence in Adult and Adolescent Rats

Alcoholism is a disorder marked by cycles of heavy drinking and chronic relapse, and adolescents are an age cohort particularly susceptible to consuming large amounts of alcohol, placing them at high risk for developing an alcohol use disorder. Adolescent humans and rats voluntarily consume more alcohol than their adult counterparts, suggesting that younger consumers of alcohol may be less sensitive to its aversive effects, which are regulated by the function of the hypothalamic-pituitary-adrenal (HPA) stress axis. While HPA axis dysfunction resulting from ethanol exposure has been extensively studied in adult animals, what happens in the adolescent brain remains largely unclear. In this study, chronic injections of ethanol was used to model alcohol dependence in adult and adolescent rats, and post-withdrawal anxiety behaviors were measured using light-dark box testing. Furthermore, corticosterone (CORT) release during treatment and after withdrawal was measured by collecting fecal and plasma samples from adults and adolescents. It was found that adults, but not adolescents, exhibit significant anxiety-like behavior following chronic ethanol withdrawal. Additionally, while the process of chronic ethanol treatment elicits an increase in day-by-day CORT release in both adults and adolescents, significantly sustained levels of CORT were not observed during withdrawal for either age group. Moreover, it was found that adults experience a longer-lasting CORT increase during chronic treatment, suggesting a larger and more robust period of dysfunction in the HPA axis for older consumers of alcohol. These results highlight CORT and glucocorticoids in general as a potential therapeutic target for treatment for alcoholism, especially that which has an onset during adolescence.

Girl in the Shadows and resilience and coping strategies in contemporary young adult fiction

The novel manuscript Girl in the Shadows tells the story of two teenage girls whose friendship, safety and sanity are pushed to the limits when an unexplained phenomenon invades their lives. Sixteen-year-old Tash has everything a teenage girl could want: good looks, brains and freedom from her busy parents. But when she looks into her mirror, a stranger’s face stares back at her. Her best friend Mal believes it’s an evil spirit and enters the world of the supernatural to find answers. But spell books and ouija boards cannot fix a problem that comes from deep within the soul. It will take a journey to the edge of madness for Tash to face the truth inside her heart and see the evil that lurks in her home. And Mal’s love and courage to pull her back into life. The exegesis examines resilience and coping strategies in adolescence, in particular, the relationship of trauma to brain development in children and teenagers. It draws on recent discoveries in neuroscience and psychology to provide a framework to examine the role of coping strategies in building resilience. Within this broader context, it analyses two works of contemporary young adult fiction, Freaky Green Eyes by Joyce Carol Oates and Sonya Hartnett’s Surrender, their use of the split persona as a coping mechanism within young adult fiction and the potential of young adult literature as a tool to help build resilience in teen readers.

Cerebellar grey-matter deficits, cannabis use and first-episode schizophrenia in adolescents and young adults

Epidemiological data link adolescent cannabis use to psychosis and schizophrenia, but its contribution to schizophrenia neuropathology remains controversial. First-episode schizophrenia (FES) patients show regional cerebral grey- and white-matter changes as well as a distinct pattern of regional grey-matter loss in the vermis of the cerebellum. The cerebellum possesses a high density of cannabinoid type 1 receptors involved in the neuronal diversification of the developing brain. Cannabis abuse may interfere with this process during adolescent brain maturation leading to ‘schizophrenia-like’ cerebellar pathology. Magnetic resonance imaging and cortical pattern matching techniques were used to investigate cerebellar grey and white matter in FES patients with and without a history of cannabis use and non-psychiatric cannabis users. In the latter group we found lifetime dose-dependent regional reduction of grey matter in the right cerebellar lobules and a tendency for more profound grey-matter reduction in lobule III with younger age at onset of cannabis use. The overall regional grey-matter differences in cannabis users were within the normal variability of grey-matter distribution. By contrast, FES subjects had lower total cerebellar grey-matter : total cerebellar volume ratio and marked grey-matter loss in the vermis, pedunculi, flocculi and lobules compared to pair-wise matched healthy control subjects. This pattern and degree of grey-matter loss did not differ from age-matched FES subjects with comorbid cannabis use. Our findings indicate small dose-dependent effects of juvenile cannabis use on cerebellar neuropathology but no evidence of an additional effect of cannabis use on FES cerebellar grey-matter pathology.

Efeitos da exposição à nicotina e/ou ao etanol durante a adolescência: alterações glutamatérgicas e na memória visuoespacial de camundongos

Adolescentes humanos frequentemente associam o fumo do tabaco ao consumo de bebidas alcoólicas. A despeito desta associação, pouco se sabe sobre a neurobiologia básica da coexposição no cérebro adolescente. No presente estudo, avaliamos os efeitos da exposição, que ocorreu do 30 ao 45 dia de vida pós natal (PN30 a PN45), à nicotina e/ou ao etanol durante a adolescência (PN38-45) e da retirada (PN50-57) na memória visuoespacial através do Labirinto Aquático de Morris (LAM: 6 sessões + 1 prova, 3 tentativas/sessão, latência = 2 min), em 4 grupos de camundongos Suíços machos e fêmeas: (1) exposição concomitante à NIC [solução de nicotina free base (50 μg/ml) em sacarina a 2% para beber] e ETOH [solução de etanol (25%, 2 g/kg) injetada i.p. em dias alternados]; (2) exposição à NIC; (3) exposição ao ETOH; (4) veículo (VEH). Uma vez que os resultados comportamentais podem sofrer a interferência de alterações motoras, avaliamos (a) a atividade locomotora no Teste de Campo Aberto (sessão única, 5 min) e (b) a coordenação e o equilíbrio no Teste de Locomoção Forçada sobre Cilindro Giratório (5 tentativas, latência = 2 min). Para os efeitos da exposição à NIC e/ou ao ETOH na eficiência do transporte de aminoácidos excitatórios, avaliamos a captação de [3H] D-aspartato no hipocampo. A expressão do transportador glial GLAST/EAAT1 foi avaliada por Western-blot. Durante a exposição, animais ETOH e NIC+ETOH apresentaram déficits de memória nas sessões de teste e de prova no LAM enquanto, na retirada, os grupos NIC e NIC+ETOH apresentaram prejuízos na retenção. Não houve diferenças significativas entre os grupos de tratamento em nenhum dos parâmetros testados em ambos os testes motores, tanto na exposição quanto na abstinência. Os grupos NIC, ETOH e NIC+ETOH tiveram uma diminuição significativa na captação de [3H] D-aspartato ao final do período de exposição, com uma normalização da atividade dos EAATs na retirada das drogas. O tratamento com NIC e ETOH reduziu ainda a expressão de GLAST/EAAT1 no hipocampo em ambas as idades testadas. O uso de etanol na adolescência causa prejuízos à memória de camundongos, com um efeito negativo mais acentuado quando associado à nicotina. Contudo, a retirada da nicotina apresentou um efeito mandatório nos danos encontrados. Ambas as drogas, isoladamente ou na coexposição, alteram os níveis de atividade e expressão dos EAATs, sugerindo que os resultados bioquímicos estejam implicados nas alterações comportamentais encontradas.

Efeitos comportamentais e endócrinos do tratamento com a vareniclina em um modelo experimental de exposição à nicotina durante a adolescência

A nicotina é considerada o principal componente psicoativo do tabaco e esta induz seus efeitos farmacológicos centrais atuando em receptores nicotínicos colinérgicos (nAChRs). A maturação dos sistemas colinérgicos é consolidada durante o período da periadolescência, o que sugere que o cérebro do adolescente é vulnerável aos efeitos de estimulantes colinérgicos. Dados os efeitos deletérios do consumo de tabaco, incluindo a dependência, têm sido desenvolvidas estratégias terapêuticas para facilitar a interrupção do uso. A mais recente é o uso da vareniclina, um agonista parcial dos nAChRs α4β2. Pouco se sabe sobre os efeitos da exposição à nicotina na adolescência e menos ainda dos efeitos de curto e longo prazos dos tratamentos disponíveis para a reversão da dependência ainda durante este período. Neste sentido, os objetivos desse trabalho foram o de estudar os comportamentos associados à ansiedade e busca por novos estímulos e a função adrenal em animais expostos à fumaça do cigarro durante a adolescência e subsequentemente tratados com procedimento para reversão de dependência à nicotina. Esse estudo utilizou 150 camundongos Suíços adolescentes (de ambos os sexos). Os animais foram expostos à solução aquosa de nicotina (50g/ml - NIC) ou de sacarina (2% - SAC) v.o. do 30o dia de vida pós-natal (PN) à PN45 e submetidos aos seguintes tratamentos por gavagem de PN45 à PN56: 1) vareniclina (0,1 ou 1,0 mg/kg/dia, VAR1 e VAR2 respectivamente); 2) veículo (VEH); 3) nicotina na dose utilizada entre PN30 e PN45 (NIC). Sete grupos experimentais foram utilizados: SACVEH, SACVAR1, SACVAR2, NICVEH, NICVAR1, NICVAR2 e NICNIC. Em PN55, os animais foram submetidos ao teste do labirinto em cruz elevado (LCE) por 5 min, e duas depois ao teste do campo vazado (CV) também por 5 min. Os tecidos coletados em PN56 (após o sacrifício dos animais) foram: adrenal esquerda para a verificação do conteúdo de catecolaminas, adrenal direita para avaliação da expressão da tirosina hidroxilase e soro para a dosagem de corticosterona. Os nossos resultados demonstraram que no final da vigência do tratamento não foram encontradas diferenças entre os grupos no comportamentos associados à ansiedade do LCE e nos associados à busca por novos estímulos no CV. Por outro lado, a análise do número de orifícios explorados no centro do CV, também utilizado como medida de ansiedade, sugerem que a vareniclina por si só e a exposição continuada à nicotina são ansiogênicas mas que que o tratamento com vareniclina após a exposição à nicotina mantém os resultados dentro da normalidade. Do ponto de vista endócrino, o conteúdo adrenal de catecolaminas foi corrigido pelo tratamento com vareniclina, os níveis séricos de corticosterona foram aumentados pela exposição à nicotina enquanto o tratamento com vareniclina aumentou a expressão de tirosina hidroxilase. Nosso estudo indica que, no final da vigência do tratamento, tanto aspectos comportamentais como endócrinos estão significativamente afetados em nosso modelo de exposição à nicotina durante a adolescência e tratamento subsequente com vareniclina. Estudos futuros deverão avaliar estes parâmetros em períodos posteriores, com o objetivo de verificar se as alterações observadas persistem na vida adulta.

Qual é o risco do consumo combinado de bebidas energéticas e etanol? Efeitos comportamentais em camundongos adolescentes

O uso combinado de etanol e bebidas energéticas tem aumentado entre adolescentes. Além disso, estudos epidemiológicos indicam que o co-uso aumenta a probabilidade de consumo abusivo e dependência de etanol. Apesar disso, pouco se sabe sobre as consequências neurocomportamentais da co-exposição no cérebro adolescente. Este estudo tem como objetivo avaliar o curso temporal dos efeitos agudos da exposição à bebida energética e/ou etanol na atividade motora e ansiedade no teste de campo aberto, como também, os efeitos agudos ou prolongados sobre aprendizagem/memória e coordenação motora em camundongos adolescentes. Camundongos Suíços foram divididos em 4 grupos: bebidas energéticas e etanol, bebida energética, etanol e água. Três estudos separados foram conduzidos para avaliar cada um dos objetivos específicos deste trabalho. No primeiro estudo, realizado em PN40, os animais receberam a administração de bebida energética (8 ml/kg) e/ou etanol (4 g/kg) por gavagem e após 55 minutos foram submetidos ao teste do campo aberto (sessão 1). Outras duas sessões foram realizadas em sequência usando a metade da dose inicial (sessão 2 e 3). Nos estudos 2 e 3, estudamos os efeitos agudos (PN40) e crônicos (exposição de PN30-40) sobre o teste de esquiva passiva (0,3 mA, 3 s) e sobre o desempenho no teste do cilíndro giratório (sessão de treinamento e após 1 e 3 horas da gavagem das drogas). Em ambos os casos, a dose de bebida energética (8 ml/kg) e/ou etanol (4 g/kg) foi administrada. No teste da esquiva passiva, as sessões de treino e retenção foram realizadas 1 e 24 horas após a administração da droga, respectivamente. No teste do Rotarod, cada sessão foi constituída por 5 tentativas em modelo de aceleramento contínuo (4 a 40 rpm/min em uma tentativa de 2 min). Os nossos dados indicam que a exposição concomitante a bebida energética potencializa o efeito de hiperatividade induzido pelo etanol, como também, gera uma resposta ansiogênica no teste do campo aberto. A exposição aguda ao etanol induz déficit de memória/aprendizagem que não é revertida pela BE. A co-exposição aguda a bebida energética e etanol prolongou incoordenação motora induzida pelo etanol. No entanto, a bebda energética reverteu o comprometimento da coordenação motora gerada pela exposição crônica de etanol em camundongos fêmeas. O presente estudo fornece evidência experimental de que bebida energética e etanol interagem durante a adolescência, resultando em padrões de comportamento que poderiam aumentar o risco de desenvolvimento de abuso ou dependência de etanol. Além disso, os dados indicaram que a exposição aguda à bebida energética não atenuou as consequências negativas geradas pela etanol no desempenho do motor e cognitivo.

Influence of different neuroprotective drugs on dopamine neurotoxicity induced by 3,4-methylenedioxymethamphetamine and MPTP in mice

Introduction: Parkinson‟s disease (PD) is characterized by a chronic progressive loss of nigrostriatal dopaminergic neurons that is associated with chronic neuroinflammation. Current treatments for PD can significantly improve symptoms but do not cure the disease or slow its progression. An approach used in existing therapies is based on the inhibition of monoamine oxidase (MAO), enzyme involved in the metabolic degradation of dopamine. Although, preclinical studies showed that MAO-B inhibitors have neuroprotective activity in cellular and animal models of PD, clinical trials did not completely confirm this result. Therefore a large number of new molecules, with more potent MAO-B inhibitory activity and a possible neuroprotective effect, have been proposed to replace the pre-existing MAO-B inhibitors. The profile of the recent MAO inhibitor, SZV558, appears to be particularly interesting because of its pharmacodynamic, favorable for disease-modifying properties and its irreversible MAO-B enzyme bind. The enhancement of adult neurogenesis could be of great clinical interest in the management of neurodegenerative disorders. In line with this, the metformin, a well-known antidiabetic drug, has recently been proposed to promote neurogenesis and to have a neuroprotective effect on the neurodegenerative processes induced by the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in a mice PD model. Although, PD has multiple origins, one hypothesis is that amphetamine-related drugs may be part of the wide array of factors leading to the dopaminergic neuron degeneration that causes the disease. These hypothesis are supported by different results that showed a persistent, long-term dopaminergic toxicity induced by 3,4-methylenedioxymethamphetamine (MDMA) in mice. Moreover, the MDMA, altering the dopaminergic transmission, may affect neurogenesis and synaptogenesis. On these basis, considering that the young brain is particularly sensitive to drug-induced neurotoxicity, the consumption of MDMA during the adolescence might increase the vulnerability of dopaminergic neurons. However, the use of amphetamine-related drugs by adolescent and young people is often combined with caffeinated energy drinks in order to amplify their stimulant actions. Although caffeine use is safe, the combined treatment of caffeine and MDMA increases not only the DA release but also the microglia and astroglia activation. Aims: During my Ph.D. I studied the influence of neuroprotective drugs, such as MAO inhibitors and metformin, or substances, such as caffeine, on the neurodegenerative effects of two dopaminergic toxins, MDMA and MPTP, in mice. 1. In the first phase of my study, I evaluated the neuroprotective activity of the new MAO-B inhibitor SZV558, compared with well-known rasagiline, in a chronic mouse model of MPTP plus probenecid (MPTPp), which induces a progressive loss of nigrostriatal dopaminergic neurons. 2. Previous results showed that when MDMA is associated with caffeine, a more pronounced degeneration in adolescent compared with adult mice was observed. To better clarify the molecular mechanism at the base of the different neurotoxic effect of this drug association at different ages, I evaluated the neuronal nitric oxide synthase (nNOS) expression, which plays a critical role in the integration of dopaminergic and glutamatergic transmissions, in the CPu of adolescent or adult mice treated with MDMA, alone or in combination with caffeine. 3. Finally, I investigated the neuroprotective effect of metformin against dopaminergic neurotoxicity induced by MDMA in the CPu and SNc of adult mice. Conclusions: These results demonstrated that the dopaminergic neurodegenerative process may be induced or conditioned by environment stressors or substances which influence, through different ways, the development of neurodegenerative mechanisms. In the present study I evaluated the effects of 3 substances, known as potentially neuroprotective, in combination with two different neurotoxins that affect the nigrostriatal dopaminergic system. The SZV558 MAO-B inhibitor and the metformin protected the nigrostriatal pathway, usually affected in PD, by MPTP- and MDMA- induced neurotoxicity, respectively. On the other hand, caffeine, administrated with MDMA, showed a neurotoxic potential depending on the age of consumers, confirming the vulnerability of adolescent brain to consumption of drug and substances that affected the dopaminergic system. In conclusion, the study of neurodegenerative processes may be relevant to understand the human pharmacology, the origin and development of neurodegenerative disease and to predict the neurotoxic effect of drug abuse.

Mutations in the MECP2 Gene Are Not a Major Cause of Rett Syndrome-Like or Related Neurodevelopmental Phenotype in Male Patients

Rett syndrome is a genetic neurodevelopmental disorder that affects mainly girls, but mutations in the causative MECP2 gene have also been identified in boys with classic Rett syndrome and Rett syndrome-like phenotypes. We have studied a group of 28 boys with a neurodevelopmental disorder, 13 of which with a Rett syndrome-like phenotype; the patients had diverse clinical presentations that included perturbations of the autistic spectrum, microcephaly, mental retardation, manual stereotypies, and epilepsy. We analyzed the complete coding region of the MECP2 gene, including the detection of large rearrangements, and we did not detect any pathogenic mutations in the MECP2 gene in these patients, in whom the genetic basis of disease remained unidentified. Thus, additional genes should be screened in this group of patients.

Adolescents, neurosciences et prise de décisions médicales: devrions-nous revoir certaines dispositions du Code civil du Québec?

Article

An untimely future for youth studies?

Peter Kelly is interested in the ways in which young people are made knowable, and governable, in relation to a range of problems that emerge in the 21st century. He illustrates where some of these trends are heading in an examination of how discourses of adolescent brain development make a powerful appearance in discussions about young people's sexuality, education, use of alcohol and drugs and their mental health. Drawing on the work of Foucault and Bauman, he questions whether the future of youth studies can be 'untimely' in the sense that it asks questions that trouble or unsettle the claims of these sorts of discourses and the various ways in which young people are made known.

Efeito do ambiente sobre o período crítico de plasticidade do córtex pré-frontal de ratos

O período crítico de plasticidade do córtex cerebral é a etapa do desenvolvimento pós-natal do sistema nervoso onde os circuitos neurais são mais suscetíveis à mudanças influenciadas por informações oriundas do ambiente. No córtex pré-frontal de humanos, responsável pelas funções executivas, o período crítico de plasticidade estende-se desde o nascimento até o final da adolescência e início da vida adulta. Isto é definido, entre outros fatores, pelo amadurecimento das redes perineuronais, uma estrutura especializada da matriz extracelular, localizada em volta do corpo celular e dendritos proximais de interneurônios inibitórios. O objetivo desta pesquisa foi verificar o efeito do ambiente em etapas distintas da adolescência sobre a estrutura e a função do córtex pré-frontal de ratos e a distribuição da expressão espacial e temporal das redes perineuronais sob estas condições. As funções executivas foram avaliadas através de testes comportamentais medindo a capacidade de memória operacional e a inibição comportamental. Observamos que estímulos estressores crônicos imprevisíveis provocam alterações no período crítico de plasticidade do córtex pré-frontal e, consequentemente, influenciam o amadurecimento das funções executivas. Observamos também que o estresse crônico induz modificação no padrão de amadurecimento das redes perineuronais no córtex pré-frontal. Estes resultados indicam a vulnerabilidade do córtex pré-frontal de ratos adolescentes para os efeitos negativos de estímulos ambientais estressores sobre o período crítico de plasticidade.