COMT Val158Met Genotype Selectively Alters Prefrontal [18F]Fallypride Displacement and Subjective Feelings of Stress in Response to a Psychosocial Stress Challenge

Catechol-O-methyltransferase (COMT) plays an essential role in degradation of extracellular dopamine in prefrontal regions of the brain. Although a polymorphism in this gene, COMT Val¹⁵⁸Met, affects human behavior in response to stress little is known about its effect on dopaminergic activity associated with the human stress response, which may be of interest for stress-related psychiatric disorders such as psychosis. We aimed to investigate the effect of variations in COMT genotype on in vivo measures of stress-induced prefrontal cortex (PFC) dopaminergic processing and subjective stress responses. A combined sample of healthy controls and healthy first-degree relatives of psychosis patients (n = 26) were subjected to an [¹⁸F]fallypride Positron Emission Tomography scan. Psychosocial stress during the scan was induced using the Montreal Imaging Stress Task and subjective stress was assessed every 12 minutes. Parametric t-maps, generated using the linear extension of the simplified reference region model, revealed an effect of COMT genotype on the spatial extent of [¹⁸F]fallypride displacement. Detected effects of exposure to psychosocial stress were unilateral and remained restricted to the left superior and right inferior frontal gyrus, with Met-hetero- and homozygotes showing less [¹⁸F]fallypride displacement than Val-homozygotes. Additionally, Met-hetero- and homozygotes experienced larger subjective stress responses than Val-homozygotes. The direction of the effects remained the same when the data was analyzed separately for controls and first-degree relatives. The human stress response may be mediated in part by COMT-dependent dopaminergic PFC activity, providing speculation for the neurobiology underlying COMT-dependent differences in human behaviour following stress. Implications of these results for stress-related psychopathology and models of dopaminergic functioning are discussed.     

Selective modifications in the nucleus accumbens of dopamine synaptic transmission in rats exposed to chronic stress

Stressful events are accompanied by modifications in dopaminergic transmission in distinct brain regions. As the activity of the neuronal dopamine (DA) transporter (DAT) is considered to be a critical mechanism for determining the extent of DA receptor activation, we investigated whether a 3-week exposure to unavoidable stress, which produces a reduction in DA output in the nucleus accumbens shell (NAcS) and medial prefrontal cortex (mPFC), would affect DAT density and DA D1 receptor complex activity in the NAcS, mPFC and caudate-putamen (CPu). Rats exposed to unavoidable stress showed a decreased DA output in the NAcS accompanied by a decrease in the number of DAT binding sites, and an increase in the number of DA D1 binding sites and Vmax of SKF 38393-stimulated adenylyl cyclase. In the mPFC, stress exposure produced a decrease in DA output with no modification in DAT binding or in DA D1 receptor complex activity. Moreover, in the CPu stress exposure induced no changes in DA output or in the other neurochemical variables examined. This study shows that exposure to a chronic unavoidable stress that produces a decrease in DA output in frontomesolimbic areas induced several adaptive neurochemical modifications selectively in the nucleus accumbens.     

Long-term behavioral and neurochemical effects of chronic stress exposure in rats

Rats exposed to acute unavoidable stress develop a deficit in escaping avoidable aversive stimuli that lasts as long as unavoidable stress exposure is repeated. A 3-week exposure to unavoidable stress also reduces dopamine (DA) output in the nucleus accumbens shell (NAcS). This study showed that a 7-day exposure to unavoidable stress induced in rats an escape deficit and a decrease in extraneuronal DA basal concentration in the NAcS. Moreover, animals had reduced DA and serotonin (5-HT) accumulation after cocaine administration in the medial pre-frontal cortex (mPFC) and NAcS, compared with control animals. After a 3-week exposure to unavoidable stress, escape deficit and reduced DA output in the NAcS were still significant at day 14 after the last stress administration. In the mPFC we observed: (i) a short-term reduction in DA basal levels that was back to control values at day 14; (ii) a decrease in DA accumulation at day 3 followed by a significant increase beyond control values at day 14; (iii) a significant reduction in 5-HT extraneuronal basal levels at day 3, but not at day 14. Finally, a significant decrease in 5-HT accumulation following cocaine administration was present in the NAcS and mPFC at day 3, but not at day 14. In conclusion, a long-term stress exposure induced long-lasting behavioral sequelae associated with reproducible neurochemical modifications.     

Regulatory effects of D2 receptors in the ventral tegmental area on the mesocorticolimbic dopaminergic pathway

To investigate the regulatory effects of somatodendritic D2 receptors on the terminal's extracellular dopamine (DA) concentration, a D2 antagonist (eticlopride) was infused directly into the ventral tegmental area via a microdialysis probe in chloral hydrate-anesthetized rats. Extracellular DA changes in both the nucleus accumbens (N ACC) and the medial prefrontal cortex (mPFC) were monitored. Infusion of 10.0 fM eticlopride had no effect on DA in the mPFC (110.2 +/- 10.0% of baseline) but significantly increased DA in the N ACC (150.1 +/- 11.7%). Infusion of a higher dose of eticlopride (100.0 or 1,000.0 fM) significantly augmented the DA in the mPFC (121.1 +/- 7.6 and 180.7 +/- 25.8%, respectively) but surprisingly had no effect on DA in the N ACC (111.5 +/- 7.3 and 104.1 +/- 8.7%, respectively). To further investigate whether the bluntness of DA increase in the N ACC was due to DA receptor activation in the mPFC, eticlopride or SCH23390 was infused into the mPFC prior to and during intrategmental eticlopride infusion, and the change of DA in the N ACC was simultaneously monitored. During intra-mPFC 1.0 nM eticlopride infusion but not during 10.0 nM SCH23390 administration (95.5 +/- 6.1%), intrategmental 1,000.0 fM eticlopride infusion could further elevate DA in the N ACC (130.0 +/- 4.6%). Our results indicated that (1) the mesolimbic and the mesocortical pathways were under tonic inhibition by somatodendritic D2 receptors; (2) the DA concentration in the N ACC first increased and then returned to baseline while the intrategmental infusion dose of eticlopride increased; and (3) the bluntness of DA increase in the N ACC resulted from the D2 receptor activation in the mPFC.     

The mGlu2/3 receptor agonist, LY354740, blocks immobilization-induced increases in noradrenaline and dopamine release in the rat medial prefrontal cortex

The metabotropic glutamate (mGlu2/3) receptor agonist, LY354740, exhibits anxiolytic-like properties in a number of rodent models. The present study utilized in vivo microdialysis to examine the effects of LY354740 on extracellular monoamine levels in the medial prefrontal cortex (mPFC) of animals subjected to 30 min immobilization stress. Immobilization stress significantly elevated extracellular levels of noradrenaline (NA) and dopamine (DA) in the mPFC, while systemic administration of LY354740 (30 mg/kg, s.c.) significantly attenuated immobilization-induced increases in both NA and DA. Reverse-dialysis of LY354740 (30 microm) into the mPFC significantly attenuated immobilization-induced increases in NA, but not DA without affecting basal levels of either amine. In separate studies in the presence of citalopram (1 microm; reverse dialysis into the mPFC), systemic administration of LY354740 attenuated immobilization-induced increases in NA and DA, but had no effect on serotonin (5-HT) levels. Co-administration of the selective mGlu2/3 receptor antagonist, LY341495, partially or fully reversed the attenuation in NA and DA levels produced by LY354740, respectively. Taken together, these data suggest that LY354740 may produce anti-stress actions, in part, by blocking stress-related increases in catecholamines in the mPFC via mGlu2/3 receptor stimulation.     

Repeated Administration of the Neurotensin Receptor Antagonist SR 48692 Differentially Regulates Mesocortical and Mesolimbic Dopaminergic Systems

Abstract: The purpose of the present study was to investigate the effects of repeated administration of the neurotensin receptor antagonist, SR 48692, on the activity of the mesocortical and mesolimbic dopaminergic (DA) systems. We showed that daily administration of SR 48692 for 15 days (1 mg/kg i.p.) to Wistar rats increased the expression of tyrosine hydroxylase mRNA and protein in the ventral mesencephalon. Simultaneous in vivo microdialysis in the shell part of the nucleus accumbens (AcbSh) and the medial prefrontal cortex (mPFC) revealed that blockade of neurotensin receptors for 15 days decreased basal extracellular levels of DA (∼50%) and its metabolites in the AcbSh, whereas no modification in DA levels was observed in the mPFC. In animals submitted to a forced swimming stress, which preferentially enhanced extracellular DA levels in the mPFC, treatment with SR 48692 failed to affect the stress-induced increase in DA. Moreover, given that glucocorticoids can modulate the activity of mesencephalic DA neurons, we examined the effect of the same SR 48692 treatment on corticosterone levels in dialysates from the AcbSh. We found that repeated SR 48692 did not affect the basal levels of free corticosterone, but significantly reduced the increase induced by forced swimming stress. The present results demonstrate that repeated treatment with SR 48692 modulates selectively the DA mesolimbic system when compared with the mesocortical pathway. These findings suggest that long-term treatment with selective neurotensin receptor antagonists could have potential clinical utility in the treatment of neuropsychiatric disorders associated with hyperactivity of the mesolimbic DA systems or the hypothalamic-pituitary-adrenal axis.     

Sleep patterns of day-working, evening high-schooled adolescents of São Paulo, Brazil

Children who grow up in developing countries of the world must work to help financially support their families, and they must also attend school. We investigated the impact of work on the sleep of working vs. nonworking high school students. Twenty-seven S?o Paulo, Brazil, public high school students (eight male and eight female working students plus six nonworking female and five nonworking male students) 14-18 yrs of age who attended school Monday-Friday between 19:00 to 22:30h participated. A comprehensive questionnaire about work and living conditions, health status, and diseases and their symptoms was also answered. The activity level and rest pattern (sleep at night and napping during the day) were continuously assessed by wrist actigraphy (Ambulatory Monitoring, USA). The main variables were analyzed by a two-factor ANOVA with application of the Tukey HSD test for multiple comparisons, and the length of sleep during weekdays vs. weekends was compared by Student t-test. Working students went to sleep earlier weekends [F(1,23)=6.1; p=0.02] and woke up earlier work days than nonworking students [F(1,23) = 17.3; p = 0.001]. The length of nighttime sleep during weekdays was shorter among all the working [F(1,23)= 16.7; p <0.001] than all the nonworking students. The sleep duration of boys was shorter than of girls during weekends [F(1,23)= 10.8; p <0.001]. During weekdays, the duration of napping by working and nonworking male students was shorter than nonworking female students. During weekdays working girls took the shortest naps [F(1,23)= 5.6; p = 0.03]. The most commonly reported sleep complaint during weekdays was difficulty waking up in the morning [F(1,23) = 6.5; p = 0.02]. During weekdays, the self-perceived sleep quality of working students was worse than nonworking students [F(1,23) = 6.2; p = 0.02]. The findings of this study show that work has negative effects on the sleep of adolescents, with the possible build-up of a chronic sleep debt with potential consequent impact on quality of life and school learning.     

Psychological processes mediating the association between developmental trauma and specific psychotic symptoms in adults: a systematic review and meta‐analysis

Experiencing psychological trauma during childhood and/or adolescence is associated with an increased risk of psychosis in adulthood. However, we lack a clear knowledge of how developmental trauma induces vulnerability to psychotic symptoms. Understanding the psychological processes involved in this association is crucial to the development of preventive interventions and improved treatments. We sought to systematically review the literature and combine findings using meta‐analytic techniques to establish the potential roles of psychological processes in the associations between developmental trauma and specific psychotic experiences (i.e., hallucinations, delusions and paranoia). Twenty‐two studies met our inclusion criteria. We found mediating roles of dissociation, emotional dysregulation and post‐traumatic stress disorder (PTSD) symptoms (avoidance, numbing and hyperarousal) between developmental trauma and hallucinations. There was also evidence of a mediating role of negative schemata, i.e. mental constructs of meanings, between developmental trauma and delusions as well as paranoia. Many studies to date have been of poor quality, and the field is limited by mostly cross‐sectional research. Our findings suggest that there may be distinct psy­chological pathways from developmental trauma to psychotic phenomena in adulthood. Clinicians should carefully ask people with psychosis about their history of developmental trauma, and screen patients with such a history for dissociation, emotional dysregulation and PTSD symptoms. Well conducted research with prospective designs, including neurocognitive assessment, is required in order to fully understand the biopsychosocial mechanisms underlying the association between developmental trauma and psychosis.     

The Association between Breast Tissue Optical Content and Mammographic Density in Pre- and Post-Menopausal Women

Mammographic density (MD), associated with higher water and lower fat content in the breast, is strongly related to breast cancer risk. Optical attenuation spectroscopy (OS) is a non-imaging method of evaluating breast tissue composition by red and near-infrared light transmitted through the breast that, unlike mammography, does not involve radiation. OS provides information on wavelength dependent light scattering of tissue and on absorption by water, lipid, oxy-, deoxy-hemoglobin. We propose that OS could be an alternative marker of breast cancer risk and that OS breast tissue measures will be associated with MD. In the present analysis, we developed an algorithm to estimate breast tissue composition and light scattering parameters using a spectrally constrained global fitting procedure employing a diffuse light transport model. OS measurements were obtained from 202 pre- and post-menopausal women with normal mammograms. Percent density (PD) and dense area (DA) were measured using Cumulus. The association between OS tissue composition and PD and DA was analyzed using linear regression adjusted for body mass index. Among pre-menopausal women, lipid content was significantly inversely associated with square root transformed PD (β = -0.05, p = 0.0002) and DA (β = -0.05, p = 0.019); water content was significantly positively associated with PD (β = 0.06, p = 0.008). Tissue oxygen saturation was marginally inversely associated with PD (β = -0.03, p = 0.057) but significantly inversely associated with DA (β = -0.10, p = 0.002). Among post-menopausal women lipid and water content were significantly associated (negatively and positively, respectively) with PD (β_lipid = -0.08, β_water = 0.14, both p<0.0001) and DA (β_lipid = -0.10, p<0.0001; β_water = 0.11, p = 0.001). The association between OS breast content and PD and DA is consistent with more proliferation in dense tissue of younger women, greater lipid content in low density tissue and higher water content in high density tissue. OS may be useful for assessing physiologic tissue differences related to breast cancer risk, particularly when mammography is not feasible or easily accessible.     

Where We Used to Live: Validating Retrospective Measures of Childhood Neighborhood Context for Life Course Epidemiologic Studies

Early life exposures influence numerous social determinants of health, as distal causes or confounders of later health outcomes. Although a growing literature is documenting how early life socioeconomic position affects later life health, few epidemiologic studies have tested measures for operationalizing early life neighborhood context, or examined their effects on later life health. In the Life-course Influences on Fetal Environments (LIFE) Study, a retrospective cohort study among Black women in Southfield, Michigan (71% response rate), we tested the validity and reliability of retrospectively-reported survey-based subjective measures of early life neighborhood context(N=693). We compared 3 subjective childhood neighborhood measures (disorder, informal social control, victimization), with 3 objective childhood neighborhood measures derived from 4 decades of historical census tract data 1970-2000, linked through geocoded residential histories (tract % poverty, tract % black, tract deprivation score derived from principal components analysis), as well as with 2 subjective neighborhood measures in adulthood. Our results documented that internal consistency reliability was high for the subjective childhood neighborhood scales (Cronbach’s α =0.89, 0.93). Comparison of subjective with objective childhood neighborhood measures found moderate associations in hypothesized directions. Associations with objective variables were strongest for neighborhood disorder (rhos=.40), as opposed to with social control or victimization. Associations between subjective neighborhood context in childhood versus adulthood were moderate and stronger for residentially-stable populations. We lastly formally tested for, but found little evidence of, recall bias of the retrospective subjective reports of childhood context. These results provide evidence that retrospective reports of subjective neighborhood context may be a cost-effective, valid, and reliable method to operationalize early life context for health studies.     

The activation of 5-HT receptors in prefrontal cortex enhances dopaminergic activity

Atypical antipsychotics show preferential 5-HT 2A versus dopamine (DA) D2 receptor affinity. At clinical doses, they fully occupy cortical 5-HT2 receptors, which suggests a strong relationship with their therapeutic action. Half of the pyramidal neurones in the medial prefrontal cortex (mPFC) express 5-HT 2A receptors. Also, neurones excited through 5-HT 2A receptors project to the ventral tegmental area (VTA). We therefore hypothesized that prefrontal 5-HT 2A receptors can modulate DA transmission through excitatory mPFC-VTA inputs. In this study we used single unit recordings to examine the responses of DA neurones to local (in the mPFC) and systemic administration of the 5-HT 2A/2C agonist 1-[2,5-dimethoxy-4-iodophenyl-2-aminopropane] (DOI). Likewise, using microdialysis, we examined DA release in the mPFC and VTA (single/dual probe) in response to prefrontal and systemic drug administration. The local (in the mPFC) and systemic administration of DOI increased the firing rate and burst firing of DA neurones and DA release in the VTA and mPFC. The increase in VTA DA release was mimicked by the electrical stimulation of the mPFC. The effects of DOI were reversed by M100907 and ritanserin. These results indicate that the activity of VTA DA neurones is under the excitatory control of 5-HT 2A receptors in the mPFC. These observations may help in the understanding of the therapeutic action of atypical antipsychotics.     

Alpha2-adrenoceptor mediated co-release of dopamine and noradrenaline from noradrenergic neurons in the cerebral cortex

Previous results suggest that extracellular dopamine (DA) in the rat cerebral cortex originates from dopaminergic and noradrenergic terminals. To further clarify this issue, dialysate DA, dihydroxyphenylacetic acid (DOPAC) and noradrenaline (NA) were measured both in the medial prefrontal cortex (mPFC) and in the occipital cortex (OCC), with dense and scarce dopaminergic projections, respectively. Moreover, the effect of the alpha2-adrenoceptor antagonist RS 79948 and the D2-receptor antagonist haloperidol on extracellular DA, DOPAC and NA was investigated. Extracellular DA and DOPAC concentrations in the OCC were 43% and 9%, respectively, those in the mPFC. Haloperidol (0.1 mg/kg i.p.) increased DA and DOPAC (by 35% and 150%, respectively) in the mPFC, but was ineffective in the OCC. In contrast, RS 79948 (1.5 mg/kg i.p.) increased NA, DA and DOPAC, both in the mPFC (by approximately 50%, 60% and 130%, respectively) and the OCC (by approximately 50%, 80% and 200%, respectively). Locally perfused, the DA transporter blocker GBR 12909 (10 micro m) was ineffective in either cortex, whereas desipramine (DMI, 100 micro m) markedly increased extracellular NA and DA in both cortices. The weak haloperidol effect on DA efflux was not enhanced after DA- and NA-transporter blockade, whereas after DMI, RS 79948 markedly increased extracellular NA, and especially DA and DOPAC in both cortices. The results support the hypothesis that most extracellular DA in the cortex is co-released with NA from noradrenergic terminals, such co-release being primarily controlled by alpha2-adrenoceptors.     

In vivo evidence that constitutive activity of serotonin2C receptors in the medial prefrontal cortex participates in the control of dopamine release in the rat nucleus accumbens: differential effects of inverse agonist versus antagonist

Control of the mesoaccumbens dopamine (DA) pathway by central serotonin_2C receptors (5-HT_2CRs) involves different 5-HT_2CR populations located within multiple brain areas. Here, using in vivo microdialysis in halothane-anesthetized rats, we assessed the role of medial prefrontal cortex (mPFC) 5-HT_2CRs in the control of basal and activated accumbal DA outflow, to identify the modalities of their recruitment and the role of 5-HT_2CR constitutive activity. Intra-mPFC injection of the 5-HT_2CR inverse agonist SB 206553 (0.5 μg/0.2 μL), without effect by itself, decreased accumbal DA outflow induced by morphine (2.5–10 mg/kg, s.c.), haloperidol (0.01 mg/kg, s.c.) or GBR 12909 (2.5 mg/kg, i.p.). Conversely, intra-mPFC injection of the 5-HT_2CR antagonist SB 242084 (0.5 μg/0.2 μL), without effect by itself, decreased the effect of 10 mg/kg morphine, the only drug enhancing basal 5-HT outflow in the mPFC. The inhibitory effect of SB 206553 on 2.5 mg/kg morphine-stimulated DA outflow was suppressed by the concomitant intra-mPFC injection of SB 242084. Finally, changes of basal DA outflow induced by the 5-HT_2CR agonist Ro 60-0175 (3 mg/kg, i.p.) or SB 206553 (5 mg/kg, i.p.) were unaffected by intra-mPFC injection of SB 242084. These results, showing that 5-HT_2CR antagonist and inverse agonist behave differently in vivo, demonstrate that mPFC 5-HT_2CRs facilitate activated accumbal DA outflow and that 5-HT_2CR constitutive activity participates in this interaction.     

Nicotine increases dopamine clearance in medial prefrontal cortex in rats raised in an enriched environment

Environmental enrichment results in differential behavioral and neurochemical responsiveness to nicotine. The present study investigates dopamine clearance (CL_DA) in striatum and medial prefrontal cortex (mPFC) using in vivo voltammetry in rats raised in enriched (EC) or impoverished conditions (IC) and administered nicotine (0.4 mg/kg) or saline. Baseline CL_DA in striatum or mPFC was not different between EC and IC. Across repeated DA application, striatal CL_DA increased in saline-control EC and IC. CL_DA increased in mPFC in saline-control IC; CL_DA did not change in saline-control EC. Thus, enrichment differentially alters dynamic responses of the dopamine transporter (DAT) to repeated DA application in mPFC, but not in striatum. In EC, nicotine increased mPFC CL_DA compared to saline-control, but had no effect on CL_DA in IC; nicotine had no effect in striatum in EC or IC. Compared to respective saline-controls, nicotine increased dihydroxyphenylacetic acid content in striatum and mPFC in EC, but not in IC. Nicotine also had no effect on DA content in striatum or mPFC in EC or IC. Results indicate that enrichment eliminated the dynamic response of mPFC DAT to repeated DA application in saline-control and augmented the nicotine-induced increase in DAT function in mPFC, but not in striatum.     

The role of the hippocampo-prefrontal cortex system in phencyclidine-induced psychosis: A model for schizophrenia

Phencyclidine (PCP) is a psychotomimetic drug that induces schizophrenia-like symptoms in healthy individuals and exacerbates pre-existing symptoms in patients with schizophrenia. PCP also induces behavioral and cognitive abnormalities in non-human animals, and PCP-treated animals are considered a reliable pharmacological model of schizophrenia. However, the exact neural mechanisms by which PCP modulates behavior are not known. During the last decade several studies have indicated that disturbed activity of the prefrontal cortex (PFC) may be closely related to PCP-induced psychosis. Systemic administration of PCP produces long-lasting activation of medial PFC (mPFC) neurons in rats, almost in parallel with augmentation of locomotor activity and behavioral stereotypies. Later studies have showed that such PCP-induced behavioral abnormalities are ameliorated by prior administration of drugs that normalize or inhibit excess excitability of PFC neurons. Similar activation of mPFC neurons is not induced by systemic injection of a typical psychostimulant such as methamphetamine, even though behavioral hyperactivity is induced to almost the same level. This suggests that the neural circuits mediating PCP-induced psychosis are different to those mediating methamphetamine-induced psychosis. Locally applied PCP does not induce excitation of mPFC neurons, indicating that PCP-induced tonic excitation of mPFC neurons is mediated by inputs from regions outside the mPFC. This hypothesis is strongly supported by experimental results showing that local perfusion of PCP in the ventral hippocampus, which has dense fiber projections to the mPFC, induces tonic activation of mPFC neurons with accompanying augmentation of behavioral abnormalities. In this review we summarize current knowledge on the neural mechanisms underlying PCP-induced psychosis and highlight a possible involvement of the PFC and the hippocampus in PCP-induced psychosis.     

Anxiety-Related Behaviours Associated with microRNA-206-3p and BDNF Expression in Pregnant Female Mice Following Psychological Social Stress

Stress during pregnancy can induce various psychological disorders in women. However, the association linking psychological stress during pregnancy with abnormal behaviours in females remains largely unknown. We employed a novel psychological stress model by introducing pregnant mice to witness the defeat process of their mated partner (WDPMP) and examined the effects of WDPMP on depression-/anxiety-like behaviours and on the expression of brain-derived neurotrophic factor (BDNF) and miR-206-3p in the hippocampus, medial prefrontal cortex (mPFC) and amygdala. Compared to pregnant control (PC) mice, pregnant stressed (PS) mice showed decreased sucrose preference during the late period of gestation, and after lactation, they spent less time in the open arms of the elevated plus maze and in the light chamber of the light/dark box. After lactation, decreased BDNF expression in both the hippocampus and mPFC of PS mice was found to be associated with enhanced miR-206-3p levels; meanwhile, elevated BDNF associated with decreased miR-206-3p expression was evident in the amygdala of the same PS mice. DNA methylation level in the Bdnf promoter did not show difference between PC and PS mice in the hippocampus. Transfection of miR-206-3p resulted in decreased BDNF levels in vitro. These results suggest that WDPMP stress during gestation can induce long-term mood alterations in pregnant mice, which may correlate with changes in miR-206-3p and BDNF expression in the hippocampus, mPFC and amygdala.     

Teen at work: the burden of a double shift on daily activities

The purpose of this study was to the evaluate time spent by working and nonworking adolescents on daily activities (work, home duties, school, transportation, other activities, leisure, sleep, and naps). Twenty-seven students, 8 male workers, 8 female workers, 5 male nonworkers, and 6 female nonworkers, ages 14-18 yrs participated in the study. They attended evening classes Monday-Friday (19:00-22:30h) in a public school in the city of S?o Paulo, Brazil. The students answered a comprehensive questionnaire on the characterization of their life, work, and health conditions. Simultaneously, they wore actigraphs (Ambulatory Monitoring, Inc.) and completed a diary of their daily activities (time spent at work, on home duties, commuting, leisure, other activities) for a minimum of 10 to a maximum of 17 consecutive days. The means of the variables were tested for differences by a two-factor (work and sex) ANOVA and Student-t test applied to pair-wise samples (weekdays and weekends). The average duration during weekdays of working time was 7 h 09 min and home duties 0 h 48 min. As for commuting time, there was a work effect [F(1,23) = 4.9; p = 0.04]; mean commuting time was 2 h 22 min for workers (males and females) and 1 h 25 min for nonworkers. There was a significant difference between workers and nonworkers [F(1,23) = 4.6; p = 0.04] regarding extra-cirricular class activities; workers spent a mean of 3 min/day on them as opposed to 1 h 14 min by nonworkers. The average daily time spent on leisure activities by workers was 6h 31 min; whereas, for nonworkers it was 7h 38min. Time spent in school amounted to 2h 47min for workers in comparison to 3h 22min by nonworkers. There was a significant work effect upon sleep [F(1,23)= 10.0; p <0.01]. The work effect upon nighttime sleep duration was significant [F(1,23)= 16.7; p <0.01]. Male workers showed a mean night sleep of 6 h 57 min and female workers 07h 15min. The average nighttime sleep duration for nonworkers was 9 h 06 min. There was a significant interactive effect between work and sex [F(1,23)= 5.6; p=0.03] for naps. Female workers showed took shortest nap on average (36 min; SD = 26 min), and female nonworkers the longest naps (1 h 45min; SD= 35min). Study and employment exert significant impact on the life and activities of high school students. Work affects sleep and nap duration plus the amount of time spent in school and other extra-curricular activities.     

6-Hydroxydopamine lesions of the medial prefrontal cortex of rats do not affect dopamine metabolism in the basal ganglia at short and long postsurgical intervals

Dopamine (DA) in the medial prefrontal cortex (mPFC) has been implicated in the regulation of subcortical DA function. To further characterize the potential interaction between cortical and subcortical DA systems, the short- and long-term neurochemical consequences of 6-hydroxydopamine (6-OHDA) lesions of the mPFC of rats were investigated in the mPFC and in its subcortical target structures. 4 to 5, 10 to 12 and 32 to 36 days after infusion of 6-OHDA, DA was depleted to a larger extent than noradrenaline and serotonin. No lesion-induced changes of DA and its metabolites were detected in subcortical structures. These results show that prefrontal 6-OHDA lesions produce immediate and long lasting depletions of prefrontal monoamines, especially of DA, without increasing basal DA metabolism in the striatum and nucleus accumbens.