Differential behavioral and neuroendocrine effects of repeated nicotine in adolescent and adult rats

Despite the high prevalence of tobacco abuse among adolescents, the neurobiology of nicotine addiction has been studied mainly in adult animals. Repeated administration of this drug to adult rats induces behavioral sensitization. Nicotine activates the HPA axis in adult rats as measured by drug-induced increases in ACTH and corticosterone. Both behavioral sensitization and corticosterone are implicated in drug addiction. We examined the expression of behavioral sensitization induced by nicotine as well as the changes in corticosterone levels after repeated injections of nicotine in adolescent and adult animals. Adolescent and adult rats received subcutaneous (s.c.) injections of saline or 0.4 mg/kg of nicotine once daily for 7 days. Three days after the last injection animals were challenged with saline or nicotine (0.4 mg/kg; s.c.). Nicotine-induced locomotion was recorded in an activity cage. Trunk blood samples were collected in a subset of adolescent and adult rats and plasma corticosterone levels were determined by radioimmunoassay. Adult, but not adolescent, rats expressed behavioral sensitization. Pretreatment with nicotine abolished corticosterone-activating effect of this drug only in adult animals, indicating the development of tolerance at this age. Our results provide evidence that adolescent rats exposed to repeated nicotine display behavioral and neuroendocrine adaptations distinct from that observed in adult animals. (c) 2004 Elsevier B.V. All rights reserved.

Cocaine-induced behavioral sensitization in adolescent rats endures until adulthood: Lack of association with GluR1 and NR1 glutamate receptor subunits and tyrosine hydroxylase

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Stress-induced reinstatement of amphetamine-conditioned place preference and changes in tyrosine hydroxylase in the nucleus accumbens in adolescent rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Independent and Combined Effects of Physical Activity and Sedentary Behavior on Blood Pressure in Adolescents: Gender Differences in Two Cross-Sectional Studies

Objectives: To examine the independent and combined association of physical activity (PA) and sedentary behavior (SB) on both systolic (SBP) and diastolic blood pressure (DBP) in adolescents from two observational studies. Methods: Participants from two cross-sectional studies, one conducted in Europe (n = 3,308; HELENA study) and the other in Brazil (n = 991; BRACAH study), were selected by complex sampling. Systolic and diastolic blood pressure (outcomes), PA and SB, both independently and combined, and potential confounders were analyzed. Associations were examined by multilevel linear regression. Results: Performing the recommended amount of PA (≥60 min/d) attenuated the effect of SB on DBP in BRACAH study girls and in boys from both studies. In contrast, PA did not attenuate the effects of SB on the SBP of girls in the HELENA study. The combination of less than recommended levels of PA with 2-4 h/d of sedentary behavior was found to be associated with increased SBP in boys from both studies. Conclusions: Meeting current PA recommendations could mediate the association between SB and DBP in both sexes. In boys, the joint effect of low levels of PA and excessive sedentary activity increases SBP levels. Longitudinal studies are required to confirm these findings. © 2013 de Moraes et al.

Metabolic risk and television time in adolescent females

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Fluoxetine exposure during pregnancy and lactation: effects on acute stress response and behavior in the novelty-suppressed feeding are age and gender-dependent in rats

Fluoxetine (FLX) is commonly used to treat anxiety and depressive disorders in pregnant women. Since FLX crosses the placenta and is excreted in milk, maternal treatment with this antidepressant may expose the fetus and neonate to increased levels of serotonin (5-HT). Long-term behavioral abnormalities have been reported in rodents exposed to higher levels of 5-HT during neurodevelopment. In this study we evaluated if maternal exposure to FLX during pregnancy and lactation would result in behavioral and/or stress response disruption in adolescent and adult rats. Our results indicate that exposure to FLX influenced restraint stress-induced Fos expression in the amygdala in a gender and age-specific manner. In male animals, a decreased expression was observed in the basolateral amygdala at adolescence and adulthood; whereas at adulthood, a decrease was also observed in the medial amygdala. A lack of FLX exposure effect was observed in females and also in the paraventricular nucleus of both genders. Regarding the behavioral evaluation, FLX exposure did not induce anhedonia in the sucrose preference test but decreased the latency to feed of both male and female adolescent rats evaluated in the novelty-suppressed feeding test. In conclusion, FLX exposure during pregnancy and lactation decreases acute amygdalar stress response to a psychological stressor in males (adolescents and adults) as well as influences the behavior of adolescents (males and females) in a model that evaluates anxiety and/or depressive-like behavior. Even though FLX seems to be a developmental neurotoxicant, the translation of these findings to human safe assessment remains to be determined since it is recognized that not treating a pregnant or lactating woman may also impact negatively the development of the descendants.

Enhancement of behavioral sensitization, anxiety-like behavior, and hippocampal and frontal cortical CREB levels following cocaine abstinence in mice exposed to cocaine during adolescence

Adolescence has been linked to greater risk-taking and novelty-seeking behavior and a higher prevalence of drug abuse and risk of relapse. Decreases in cyclic adenosine monophosphate response element binding protein (CREB) and phosphorylated CREB (pCREB) have been reported after repeated cocaine administration in animal models. We compared the behavioral effects of cocaine and abstinence in adolescent and adult mice and investigated possible age-related differences in CREB and pCREB levels. Adolescent and adult male Swiss mice received one daily injection of saline or cocaine (10 mg/kg, i.p.) for 8 days. On day 9, the mice received a saline injection to evaluate possible environmental conditioning. After 9 days of withdrawal, the mice were tested in the elevated plus maze to evaluate anxiety-like behavior. Twelve days after the last saline/cocaine injection, the mice received a challenge injection of either cocaine or saline, and locomotor activity was assessed. One hour after the last injection, the brains were extracted, and CREB and pCREB levels were evaluated using Western blot in the prefrontal cortex (PFC) and hippocampus. The cocaine-pretreated mice during adolescence exhibited a greater magnitude of the expression of behavioral sensitization and greater cocaine withdrawal-induced anxiety-like behavior compared with the control group. Significant increases in CREB levels in the PFC and hippocampus and pCREB in the hippocampus were observed in cocaine-abstinent animals compared with the animals treated with cocaine in adulthood. Interestingly, significant negative correlations were observed between cocaine sensitization and CREB levels in both regions. These results suggest that the behavioral and neurochemical consequences of psychoactive substances in a still-developing nervous system can be more severe than in an already mature nervous system

Similar ethanol drinking in adolescent and adult C57BL/6J mice after chronic ethanol exposure and withdrawal

BACKGROUND: Increasing evidence shows that excessive alcohol consumption during adolescence increases vulnerability to alcohol use disorders in adulthood. The aim of this study was to examine differences between adolescent and adult C57BL/6J mice in drinking behavior and blood ethanol (EtOH) concentrations (BECs) after chronic EtOH exposure and withdrawal. METHODS: Male adolescent (PND = 28 to 30) and adult (PND = 70) C57BL/6J mice were allowed to consume EtOH in a 2-bottle choice paradigm (15% EtOH vs. water) for 3 weeks (Baseline drinking, Test 1, and Test 2), which were interspersed with 2 cycles (Cycles I and II) of chronic EtOH vapor or air inhalation (16 hours) and withdrawal (8 hours). BECs were determined during both cycles. RESULTS: Chronic EtOH exposure led to increased EtOH intake during Test 1 and Test 2 in both adolescent and adult mice compared with air-exposed controls, and no differences between age groups were observed. During Cycle I adult mice showed higher BECs compared with adolescents. During Cycle II, BECs were lower in adult mice as compared to Cycle I, and BECs in adolescent mice did not change between the 2 cycles. CONCLUSIONS: Chronic EtOH exposure followed by withdrawal periods increases EtOH consumption similarly in both adolescent and adult mice, despite differences in BECs

Intraoperative determination of the load-displacement behavior of scoliotic spinal motion segments: preliminary clinical results

Introduction: Spinal fusion is a widely and successfully performed strategy for the treatment of spinal deformities and degenerative diseases. The general approach has been to stabilize the spine with implants so that a solid bony fusion between the vertebrae can develop. However, new implant designs have emerged that aim at preservation or restoration of the motion of the spinal segment. In addition to static, load sharing principles, these designs also require a profound knowledge of kinematic and dynamic properties to properly characterise the in vivo performance of the implants. Methods: To address this, an apparatus was developed that enables the intraoperative determination of the load–displacement behavior of spinal motion segments. The apparatus consists of a sensor-equipped distractor to measure the applied force between the transverse processes, and an optoelectronic camera to track the motion of vertebrae and the distractor. In this intraoperative trial, measurements from two patients with adolescent idiopathic scoliosis with right thoracic curves were made at four motion segments each. Results: At a lateral bending moment of 5 N m, the mean flexibility of all eight motion segments was 0.18 ± 0.08°/N m on the convex side and 0.24 ± 0.11°/N m on the concave side. Discussion: The results agree with published data obtained from cadaver studies with and without axial preload. Intraoperatively acquired data with this method may serve as an input for mathematical models and contribute to the development of new implants and treatment strategies.

Dimensions of impulsive behavior in adolescents: laboratory behavioral assessments

Impulsivity is a multifaceted construct that defines a range of maladaptive behavioral styles. The present research aimed to identify different dimensions of impulsive behavior in adolescents from a battery of laboratory behavioral assessments. In one analysis, correlations were examined between two self report and seven laboratory behavioral measures of impulsivity. The correlation between the two self report measures was high compared to correlations between the self report and laboratory behavioral measures. In a second analysis, a principal components analysis was performed with just the laboratory behavioral measures. Three behavioral dimensions were identified -- "impulsive decision-making", "impulsive inattention", and "impulsive disinhibition". These dimensions were further evaluated using the same sample with a confirmatory factor analysis, which did support the hypothesis that these are significant and independent dimensions of impulsivity. This research indicates there are at least three separate subtypes of impulsive behavior when using laboratory behavioral assessments with adolescent participants.

Acute and chronic methylphenidate dose-response assessment on three adolescent male rat strains.

Methylphenidate (MPD), commonly known as Ritalin, is the most frequently prescribed drug to treat children and adults with attention deficit hyperactivity disorder (ADHD). Adolescence is a period of development involving numerous neuroplasticities throughout the central nervous system (CNS). Exposure to a psychostimulant such as MPD during this crucial period of neurodevelopment may cause transient or permanent changes in the CNS. Genetic variability may also influence these differences. Thus, the objective of the present study was to determine whether acute and chronic administration of MPD (0.6, 2.5, or 10.0mg/kg, i.p.) elicit effects among adolescent WKY, SHR, and SD rats and to compare whether there were strain differences. An automated, computerized, open-field activity monitoring system was used to study the dose-response characteristics of acute and repeated MPD administration throughout the 11-day experimental protocol. Results showed that all three adolescent rat groups exhibited dose-response characteristics following acute and chronic MPD administration, as well as strain differences. These strain differences depended on the MPD dose and locomotor index. Chronic treatment of MPD in these animals did not elicit behavioral sensitization, a phenomenon described in adult rats that is characterized by the progressive augmentation of the locomotor response to repeated administration of the drug. These results suggest that the animal's age at time of drug treatment and strain/genetic variability play a crucial role in the acute and chronic effect of MPD and in the development of behavioral sensitization.

The adolescent response to pregnancy: Accepting the reality

The research literature on adolescent pregnancy indicates a relationship between early prenatal care and positive pregnancy outcomes, yet fewer than half of pregnant teenagers seek prenatal care in the first trimester of pregnancy. Although social support theory speculates that there should be a relationship between support and health outcomes, available studies do not reflect the processes by which pregnant adolescents use their social resources in making decisions about their pregnancies. This study describes the processes by which the adolescent comes to accept the reality of her pregnancy.^ Drawing from the social-psychological theories of illness behavior and symbolic interactionism, this study examines the symptom diagnosis and help seeking behavior of the pregnant adolescent. This approach describes how the adolescent interprets events and draws conclusions based on her social reality.^ Interviews were conducted with ten young women, aged 15-17, who had recently delivered a first child. Onset of prenatal care ranged from the third month to the seventh month. None were married, and all but two lived with a parent. All but one were currently in school. Initial unstructured interviews were attempted to construe the modes of expression of the young women regarding the event of pregnancy. Subsequent interviews elicited the processes of recognition and explanation of symptoms of pregnancy.^ Analysis revealed a consistent natural history in the subjects' experiences as they come to accept the reality of pregnancy. Symptom appraisal and definition involves noticing changes in themselves, and evaluating and attempting to find suitable explanations for these symptoms. Lay consultation from friends and family aids in identifying the symptoms and to receive suggestions for treatment. It is at this point that prenatal care is usually initiated. Finally the young women describe the integration of pregnancy into their belief systems. ^

Project Alpha: A culturally appropriate approach to adolescent male sex education

In the United States today, adolescents face unacceptably high rates of mortality and morbidity due to the contraction of HIV/AIDS, sexually transmitted diseases and teenage pregnancy. In view of these rates, there is a need for applied preventive interventions to delay adolescent sexual behavior until adulthood. Project Alpha was a school-adopted, quasi-experimental program for adolescent male students attending Sharpstown High School in Houston, Texas. This intervention used student newsletters to provide specific role-model stories on community and student role models who have changed attitudes or improved efficacy to abstain from sexual behavior until adulthood. It was hypothesized that teenagers exposed to the intervention would show improvements in knowledge, beliefs, avoidance skills, perceived norms, intentions and self-efficacy to delay sexual behavior compared to no-treatment reference teenagers in the same school.^ In total, the Project Alpha program had a significant effect on student knowledge, beliefs (towards abstinence and having sex with multiple partners), perceived risk (HIV/STD testing), self-efficacy (could avoid sex with attractive girl who wants to have sex), perceived social norms (friends believing in sexual abstinence) and sexual intentions. However, no significant intervention effects were found in student's beliefs (that it was OK to have sex with girlfriend), perceived risk of HIV/STD, self-efficacy (to avoid sex with girlfriend) and social norms (friends believe it is OK to have sex with a girlfriend and multiple partners in the same month). ^

Axial suspension test to assess pre-operative spinal flexibility in patients with adolescent idiopathic scoliosis.

INTRODUCTION An accurate description of the biomechanical behavior of the spine is crucial for the planning of scoliotic surgical correction as well as for the understanding of degenerative spine disorders. The current clinical assessments of spinal mechanics such as side-bending or fulcrum-bending tests rely on the displacement of the spine observed during motion of the patient. Since these tests focused solely on the spinal kinematics without considering mechanical loads, no quantification of the mechanical flexibility of the spine can be provided. METHODS A spinal suspension test (SST) has been developed to simultaneously monitor the force applied on the spine and the induced vertebral displacements. The system relies on cervical elevation of the patient and orthogonal radiographic images are used to measure the position of the vertebras. The system has been used to quantify the spinal flexibility on five AIS patients. RESULTS Based on the SST, the overall spinal flexibility varied between 0.3 °/Nm for the patient with the stiffer curve and 2 °/Nm for the less rigid curve. A linear correlation was observed between the overall spinal flexibility and the change in Cobb angle. In addition, the segmental flexibility calculated for five segments around the apex was 0.13 ± 0.07 °/Nm, which is similar to intra-operative stiffness measurements previously published. CONCLUSIONS In summary, the SST seems suitable to provide pre-operative information on the complex functional behavior and stiffness of spinal segments under physiological loading conditions. Such tools will become increasingly important in the future due to the ever-increasing complexity of the surgical instrumentation and procedures.

Predictors for DSM-5 nonsuicidal self-injury in female adolescent inpatients: The role of childhood maltreatment, alexithymia, and dissociation

The purpose of this study was to examine the relationship between various adverse childhood experiences, alexithymia, and dissociation in predicting nonsuicidal self-injury (NSSI) in an inpatient sample of female adolescents. Seventy-two adolescents (aged 14–18 years) with NSSI disorder (n=46) or mental disorders without NSSI (n=26) completed diagnostic interviews and self-report measures to assess NSSI disorder according to the DSM-5 criteria, childhood maltreatment, alexithymia, and dissociation. Alexithymia and dissociation were highly prevalent in both study groups. Multivariate logistic regression analyses indicated that only alexithymia was a significant predictor for NSSI, whereas childhood maltreatment and dissociation had no predictive influence. The association between alexithymia and NSSI emphasizes the significance of emotion regulation training for female adolescents with NSSI. Efforts to reduce NSSI behavior should therefore foster skills to heighten the perception and recognition of one’s own emotions.