Cosmic Birefringence from the Planck Data Release 4.

We search for the signature of parity-violating physics in the cosmic microwave background, called cosmic birefringence, using the Planck data release 4. We initially find a birefringence angle of ß=0.30°±0.11° (68% C.L.) for nearly full-sky data. The values of ß decrease as we enlarge the Galactic mask, which can be interpreted as the effect of polarized foreground emission. Two independent ways to model this effect are used to mitigate the systematic impact on ß for different sky fractions. We choose not to assign cosmological significance to the measured value of ß until we improve our knowledge of the foreground polarization.

Aberrant development of intrinsic brain activity in a rat model of caregiver maltreatment of offspring.

Caregiver maltreatment induces vulnerability to later-life psychopathology. Clinical and preclinical evidence suggest changes in prefrontal and limbic circuitry underlie this susceptibility. We examined this question using a rat model of maternal maltreatment and methods translated from humans, resting-state functional magnetic resonance imaging (R-fMRI). Rat pups were reared by mothers provided with insufficient or abundant bedding for nest building from postnatal (PN) days 8 to 12 and underwent behavioral assessments of affect-related behaviors (forced swim, sucrose preference and social interaction) in adolescence (PN45) and early adulthood (PN60). R-fMRI sessions were conducted under light anesthesia at both ages. Offspring reared with insufficient bedding (that is, maltreated) displayed enduring negative affective behaviors. Amygdala-prefrontal cortex (PFC) functional connectivity increased significantly from adolescence to adulthood in controls, but not in maltreated animals. We computed the fractional amplitude of low-frequency fluctuations (fALFF), an index of intrinsic brain activity, and found that fALFF in medial prefrontal cortex and anterior cingulate cortex (MPFC/ACC) increased significantly with age in controls but remained unchanged in maltreated animals during adolescence and adulthood. We used a seed-based analysis to explore changes in functional connectivity between this region and the whole brain. Compared with controls, maltreated animals demonstrated reduced functional connectivity between MPFC/ACC and left caudate/putamen across both ages. Functional connectivity between MPFC/ACC and right caudate/putamen showed a group by age interaction: decreased in controls but increased in maltreated animals. These data suggest that maltreatment induces vulnerability to psychopathology and is associated with differential developmental trajectories of prefrontal and subcortical circuits underlying affect regulation.

Emergence of social behavior deficit, blunted corticolimbic activity and adult depression-like behavior in a rodent model of maternal maltreatment.

Disrupted social behavior is a core symptom of multiple psychiatric and neurodevelopmental disorders. Many of these disorders are exacerbated by adverse infant experiences, including maltreatment and abuse, which negatively affect amygdala development. Although a link between impaired social behavior, abnormal amygdala function and depressive-like behavior following early adversity has been demonstrated in humans and animal models, the developmental emergence of maltreatment-related social deficits and associated amygdala neural activity are unknown. We used a naturalistic rodent model of maternal maltreatment during a sensitive period, postnatal days 8-12 (PN8-12), which produces social behavior deficits that precede adolescent depressive-like behavior and amygdala dysfunction, to examine social behavior in infancy, periweaning and adolescence. Neural activity in response to the social behavior test was assessed via c-Fos immunohistochemistry at these ages. A separate group of animals was tested for adult depressive-like behavior in the forced swim test. Maltreatment spared infant (PN16-18) social behavior but disrupted periweaning (PN20-22) and adolescent (PN42-48) social behavior. Maltreated rats exhibited blunted neural activation in the amygdala and other areas implicated in social functioning, including the medial prefrontal cortex and nucleus accumbens, at these ages and increased adult depressive-like behavior. These findings may suggest corticolimbic involvement in the emergence of maltreatment-induced social deficits that are linked to adult depressive-like behavior, thereby highlighting potential targets for therapeutic intervention. Understanding how infant experiences influence social behavior and age-specific expression across development may provide insights into basic neural mechanisms of social behaviors and disease-relevant social dysfunction exacerbated by early-life stress.

Developmental emergence of fear/threat learning: neurobiology, associations and timing.

Pavlovian fear or threat conditioning, where a neutral stimulus takes on aversive properties through pairing with an aversive stimulus, has been an important tool for exploring the neurobiology of learning. In the past decades, this neurobehavioral approach has been expanded to include the developing infant. Indeed, protracted postnatal brain development permits the exploration of how incorporating the amygdala, prefrontal cortex and hippocampus into this learning system impacts the acquisition and expression of aversive conditioning. Here, we review the developmental trajectory of these key brain areas involved in aversive conditioning and relate it to pups' transition to independence through weaning. Overall, the data suggests that adult-like features of threat learning emerge as the relevant brain areas become incorporated into this learning. Specifically, the developmental emergence of the amygdala permits cue learning and the emergence of the hippocampus permits context learning. We also describe unique features of learning in early life that block threat learning and enhance interaction with the mother or exploration of the environment. Finally, we describe the development of a sense of time within this learning and its involvement in creating associations. Together these data suggest that the development of threat learning is a useful tool for dissecting adult-like functioning of brain circuits, as well as providing unique insights into ecologically relevant developmental changes.

Mesocortical dopamine depletion and anxiety-related behavior in the rat: sex and hemisphere differences.

The mesocortical dopamine (DA) system of the rat plays an important role in prefrontal cortex (PFC) regulation of stress and emotion and exhibits functional hemispheric asymmetry for such processing. Since few studies examine sex differences in this context, we compared the effects of left vs. right unilateral PFC DA depletion in males and females in several behavioral situations associated with anxiety or aversion. Adult rats received unilateral injections of 6-hydroxydopamine (6-OHDA) or vehicle in the ventromedial (vm) PFC. Behavioral tests included a predator odor burying test, elevated plus maze and sucrose consumption with simple taste aversion. Tissue analysis confirmed that vmPFCs injected with 6-OHDA were depleted of DA (75-85%) compared to controls. Burying behavior and sucrose consumption were affected only by left lesions, similarly in both sexes. However, risk assessment behaviors were affected by right lesions in opposite directions in males and females. Behaviors modified preferentially by the left cortex thus showed less evidence of sex differences than those modulated by the right. While mesocortical DA depletion effects are lateralized, the nature of these effects can vary with sex and specific behavior. Such findings may be clinically significant, given the large gender differences in the incidence of mood and anxiety disorders, which also show many lateralized prefrontal abnormalities.

An experiment on the dynamics of ion implantation and sputtering of surfaces.

A major impediment towards a better understanding of the complex plasma-surface interaction is the limited diagnostic access to the material surface while it is undergoing plasma exposure. The Dynamics of ION Implantation and Sputtering Of Surfaces (DIONISOS) experiment overcomes this limitation by uniquely combining powerful, non-perturbing ion beam analysis techniques with a steady-state helicon plasma exposure chamber, allowing for real-time, depth-resolved in situ measurements of material compositions during plasma exposure. Design solutions are described that provide compatibility between the ion beam analysis requirements in the presence of a high-intensity helicon plasma. The three primary ion beam analysis techniques, Rutherford backscattering spectroscopy, elastic recoil detection, and nuclear reaction analysis, are successfully implemented on targets during plasma exposure in DIONISOS. These techniques measure parameters of interest for plasma-material interactions such as erosion/deposition rates of materials and the concentration of plasma fuel species in the material surface.

Unpredictable neonatal stress enhances adult anxiety and alters amygdala gene expression related to serotonin and GABA.

Anxiety-related disorders are among the most common psychiatric illnesses, thought to have both genetic and environmental causes. Early-life trauma, such as abuse from a caregiver, can be predictable or unpredictable, each resulting in increased prevalence and severity of a unique set of disorders. In this study, we examined the influence of early unpredictable trauma on both the behavioral expression of adult anxiety and gene expression within the amygdala. Neonatal rats were exposed to unpaired odor-shock conditioning for 5 days, which produces deficits in adult behavior and amygdala dysfunction. In adulthood, we used the Light/Dark box test to measure anxiety-related behaviors, measuring the latency to enter the lit area and quantified urination and defecation. The amygdala was then dissected and a microarray analysis was performed to examine changes in gene expression. Animals that had received early unpredictable trauma displayed significantly longer latencies to enter the lit area and more defecation and urination. The microarray analysis revealed over-represented genes related to learning and memory, synaptic transmission and trans-membrane transport. Gene ontology and pathway analysis identified highly represented disease states related to anxiety phenotypes, including social anxiety, obsessive-compulsive disorders, post-traumatic stress disorder and bipolar disorder. Addiction-related genes were also overrepresented in this analysis. Unpredictable shock during early development increased anxiety-like behaviors in adulthood with concomitant changes in genes related to neurotransmission, resulting in gene expression patterns similar to anxiety-related psychiatric disorders.

Neurobiology of secure infant attachment and attachment despite adversity: a mouse model.

Attachment to an abusive caregiver has wide phylogenetic representation, suggesting that animal models are useful in understanding the neural basis underlying this phenomenon and subsequent behavioral outcomes. We previously developed a rat model, in which we use classical conditioning to parallel learning processes evoked during secure attachment (odor-stroke, with stroke mimicking tactile stimulation from the caregiver) or attachment despite adversity (odor-shock, with shock mimicking maltreatment). Here we extend this model to mice. We conditioned infant mice (postnatal day (PN) 7-9 or 13-14) with presentations of peppermint odor and either stroking or shock. We used (14) C 2-deoxyglucose (2-DG) to assess olfactory bulb and amygdala metabolic changes following learning. PN7-9 mice learned to prefer an odor following either odor-stroke or shock conditioning, whereas odor-shock conditioning at PN13-14 resulted in aversion/fear learning. 2-DG data indicated enhanced bulbar activity in PN7-9 preference learning, whereas significant amygdala activity was present following aversion learning at PN13-14. Overall, the mouse results parallel behavioral and neural results in the rat model of attachment, and provide the foundation for the use of transgenic and knockout models to assess the impact of both genetic (biological vulnerabilities) and environmental factors (abusive) on attachment-related behaviors and behavioral development.

Role of sex in the neurochemical and neuroendocrine correlates of paw preference in the rat.

Handedness in humans and paw preference (PP) in rodents have been associated with neural and physiological correlates, which frequently appear to be sex-specific. The present study examines sex differences in the effects of differential PP on post mortem measures of regional monoamine activity in adult Long-Evans rats. The effects of PP on neuroendocrine function were also assessed by measuring plasma adrenocorticotropic hormone (ACTH) in response to a 30-min restraint stress. Most rats showed strong individual PP. Males (n=27) and females (n=26) did not differ in the direction or strength of their PP with nearly equal numbers of left and right-pawed rats. However, many Sex×PP interactions were noted in regional neurochemical measures, and most effects of PP were bilateral in nature and sex-specific. In males, Left PP (relative to Right PP) was associated with reduced striatal dopamine (DA) levels and amygdala DA metabolism bilaterally. In females, Left PP was associated with a bilateral upregulation of DAergic metabolism in both prefrontal cortex and nucleus accumbens, increased amygdala serotonin metabolism, and a (right) unilateral increase in amygdala DA. As in previous studies, some correlations were also noted between PP and asymmetrical or unilateral monoamine measures. As well, rats with strong PP, independent of direction or sex, had lower basal ACTH and more robust stress responses than rats with weak PP, suggesting a possible adaptive advantage to strong lateralization. Overall, sex differences were found only regarding effects of the direction of PP, not its magnitude. The findings suggest that the direction of PP affects distinct bilateral networks of structures sex-dependently. Such fundamental influences of PP on functional brain organization have implications for a wide array of processes under monoaminergic modulation in these brain regions, and may further our understanding of the numerous human examples of gender and handedness interactions across several modalities.

Association analysis of 31 common polymorphisms with type 2 diabetes and its related traits in Indian sib pairs.

AIMS/HYPOTHESIS: Evaluation of the association of 31 common single nucleotide polymorphisms (SNPs) with fasting glucose, fasting insulin, HOMA-beta cell function (HOMA-ß), HOMA-insulin resistance (HOMA-IR) and type 2 diabetes in the Indian population. METHODS: We genotyped 3,089 sib pairs recruited in the Indian Migration Study from four cities in India (Lucknow, Nagpur, Hyderabad and Bangalore) for 31 SNPs in 24 genes previously associated with type 2 diabetes in European populations. We conducted within-sib-pair analysis for type 2 diabetes and its related quantitative traits. RESULTS: The risk-allele frequencies of all the SNPs were comparable with those reported in western populations. We demonstrated significant associations of CXCR4 (rs932206), CDKAL1 (rs7756992) and TCF7L2 (rs7903146, rs12255372) with fasting glucose, with ß values of 0.007 (p = 0.05), 0.01 (p = 0.01), 0.007 (p = 0.05), 0.01 (p = 0.003) and 0.08 (p = 0.01), respectively. Variants in NOTCH2 (rs10923931), TCF-2 (also known as HNF1B) (rs757210), ADAM30 (rs2641348) and CDKN2A/B (rs10811661) significantly predicted fasting insulin, with ß values of -0.06 (p = 0.04), 0.05 (p = 0.05), -0.08 (p = 0.01) and -0.08 (p = 0.02), respectively. For HOMA-IR, we detected associations with TCF-2, ADAM30 and CDKN2A/B, with ß values of 0.05 (p = 0.04), -0.07 (p = 0.03) and -0.08 (p = 0.02), respectively. We also found significant associations of ADAM30 (ß = -0.05; p = 0.01) and CDKN2A/B (ß = -0.05; p = 0.03) with HOMA-ß. THADA variant (rs7578597) was associated with type 2 diabetes (OR 1.5; 95% CI 1.04, 2.22; p = 0.03). CONCLUSIONS/INTERPRETATION: We validated the association of seven established loci with intermediate traits related to type 2 diabetes in an Indian population using a design resistant to population stratification.

Associations of FTO and MC4R Variants with Obesity Traits in Indians and the Role of Rural/Urban Environment as a Possible Effect Modifier.

Few studies have investigated the association between genetic variation and obesity traits in Indian populations or the role of environmental factors as modifiers of these relationships. In the context of rapid urbanisation, resulting in significant lifestyle changes, understanding the aetiology of obesity is important. We investigated associations of FTO and MC4R variants with obesity traits in 3390 sibling pairs from four Indian cities, most of whom were discordant for current dwelling (rural or urban). The FTO variant rs9939609 predicted increased weight (0.09 Z-scores, 95% CI: 0.03, 0.15) and BMI (0.08 Z-scores, 95% CI: 0.02, 0.14). The MC4R variant rs17782313 was weakly associated with weight and hip circumference (P < .05). There was some indication that the association between FTO and weight was stronger in urban than that in rural dwellers (P for interaction = .03), but no evidence for effect modification by diet or physical activity. Further studies are needed to investigate ways in which urban environment may modify genetic risk of obesity.

The neurobiology of infant maternal odor learning

Infant rats must learn to identify their mother’s diet-dependent odor. Once learned, maternal odor controls pups’ approach to the mother, their social behavior and nipple attachment. Here we present a review of the research from four different laboratories, which suggests that neural and behavioral responses to the natural maternal odor and neonatal learned odors are similar. Together, these data indicate that pups have a unique learning circuit relying on the olfactory bulb for neural plasticity and on the hyperfunctioning noradrenergic locus coeruleus flooding the olfactory bulb with norepinephrine to support the neural changes. Another important factor making this system unique is the inability of the amygdala to become incorporated into the infant learning circuit. Thus, infant rats appear to be primed in early life to learn odors that will evoke approach responses supporting attachment to the caregiver.

The neurobiology of infant maternal odor learning.

Infant rats must learn to identify their mother's diet-dependent odor. Once learned, maternal odor controls pups' approach to the mother, their social behavior and nipple attachment. Here we present a review of the research from four different laboratories, which suggests that neural and behavioral responses to the natural maternal odor and neonatal learned odors are similar. Together, these data indicate that pups have a unique learning circuit relying on the olfactory bulb for neural plasticity and on the hyperfunctioning noradrenergic locus coeruleus flooding the olfactory bulb with norepinephrine to support the neural changes. Another important factor making this system unique is the inability of the amygdala to become incorporated into the infant learning circuit. Thus, infant rats appear to be primed in early life to learn odors that will evoke approach responses supporting attachment to the caregiver.

Effects of unilateral amygdala dopamine depletion on behaviour in the elevated plus maze: role of sex, hemisphere and retesting.

A growing body of literature suggests that sex differences exist in both rodents and humans in terms of the central processing of stress and emotion, and an important factor in this regard may involve differential hemispheric specialization. The amygdala has been shown to be functionally asymmetrical in both rats and humans and its involvement in stress and emotion processing is well documented. Given that amygdala function is importantly modulated by dopamine (DA), the present study examined the effects of left vs. right unilateral DAergic depletion targeting the basolateral amygdala in male and female rats. We examined behaviour in the elevated plus maze over two consecutive days, and plasma adrenocorticotropic hormone (ACTH) levels in response to a separate 30min restraint stress. Overall, females showed significantly more exploration of open arms of the plus maze than males, while not differing in general activity reflected in closed arm entries. Significant SexxHemisphere interactions were observed for all measures related to open arm exploration, as right amygdala DA depletion produced an anxiolytic effect in males, increasing open arm exploration, but reduced this behaviour in females. Moreover, open arm exploration was greatly reduced on the second maze exposure in males, but unchanged in females. A SexxHemisphere interaction was also found for plasma ACTH levels. It is suggested that the role of amygdala DA on stress-related behaviour and physiology reflects inherent differences in amygdala function dependent on both sex and hemisphere.

Long-term colonic hypersensitivity in adult rats induced by neonatal unpredictable vs predictable shock.

Our goal was to examine the relationship between early life trauma and the development of visceral hypersensitivity in later life in irritable bowel syndrome (IBS). Rat pups underwent neonatal conditioning: (i) paired odour-shock, where odour is a predictable shock signal, (ii) unpaired odour-shock, where odour is an unpredictable shock signal or (iii) control odour-only with odour presentations and handling without shock. At maturity, colorectal sensitivity was measured as a visceromotor behavioural response. In adulthood, colorectal distension (CRD) induced a pressure-dependent increase in the number of abdominal muscle contractions all three experimental groups. However, compared to animals that had received control odour-only presentations in infancy, there was an attenuated response to CRD in animals previously exposed to neonatal predictable shock pups and an exaggerated response in the animals previously exposed to neonatal unpredictable shock. Adult responses to CRD were altered by infant experience with shock trauma. However, depending on the context of that early life trauma, there are major differences between the long-term effects of that early life trauma on colonic sensitivity compared to controls. These results strengthen the link between early life trauma and adult IBS, and suggest that unpredictable trauma is a critical factor for later life disorders.

Proteomic analysis of human meibomian gland secretions.

BACKGROUND/AIM: Human tears contain hundreds of proteins that may exert a significant influence on tear film stability, ocular surface integrity, and visual function. The authors hypothesise that many of these proteins originate from the meibomian gland. This study's aim was to begin to develop the proteomic methodology to permit the testing of their hypothesis. METHODS: Meibomian gland secretions were collected from the lower eyelids of adult volunteers and placed in a chloroform-methanol mixture. Samples were partitioned in a biphasic system and non-lipid phase materials were reduced, alkylated, and trypsin digested to obtain peptides for protein identification. This peptide mixture was separated by micro-capillary reverse phase chromatography and the effluent examined by nano-electrospray MS and data dependent MS/MS. SEQUEST software was used to identify proteins from the MS/MS spectra. RESULTS: The methodological approach to date has permitted the identification of more than 90 proteins in human meibomian gland secretions. Proteins include the alpha2-macroglobulin receptor, IgA alpha chain, farnesoid X activated receptor, interferon regulatory factor 3, lacritin precursor, lactotransferrin, lipocalin 1, lysozyme C precursor, potential phospholipid transporting ATPase IK, seven transmembrane helix receptor (also termed somatostatin receptor type 4), testes development related NYD-SP21 (also termed high affinity IgE receptor beta subunit), and TrkC tyrosine kinase. CONCLUSIONS: These findings indicate that the meibomian gland secretes a number of proteins into the tear film. It is quite possible that these proteins contribute to the dynamics of the tear film in both health and disease.

Plasticity in the olfactory system: lessons for the neurobiology of memory.

We are rapidly advancing toward an understanding of the molecular events underlying odor transduction, mechanisms of spatiotemporal central odor processing, and neural correlates of olfactory perception and cognition. A thread running through each of these broad components that define olfaction appears to be their dynamic nature. How odors are processed, at both the behavioral and neural level, is heavily dependent on past experience, current environmental context, and internal state. The neural plasticity that allows this dynamic processing is expressed nearly ubiquitously in the olfactory pathway, from olfactory receptor neurons to the higher-order cortex, and includes mechanisms ranging from changes in membrane excitability to changes in synaptic efficacy to neurogenesis and apoptosis. This review will describe recent findings regarding plasticity in the mammalian olfactory system that are believed to have general relevance for understanding the neurobiology of memory.

Hemispheric asymmetry in stress processing in rat prefrontal cortex and the role of mesocortical dopamine.

The prefrontal cortex (PFC) is known to play an important role not only in the regulation of emotion, but in the integration of affective states with appropriate modulation of autonomic and neuroendocrine stress regulatory systems. The present review highlights findings in the rat which helps to elucidate the complex nature of prefrontal involvement in emotion and stress regulation. The medial PFC is particularly important in this regard and while dorsomedial regions appear to play a suppressive role in such regulation, the ventromedial (particularly infralimbic) region appears to activate behavioral, neuroendocrine and sympathetic autonomic systems in response to stressful situations. This may be especially true of spontaneous stress-related behavior or physiological responses to relatively acute stressors. The role of the medial PFC is somewhat more complex in conditions involving learned adjustments to stressful situations, such as the extinction of conditioned fear responses, but it is clear that the medial PFC is important in incorporating stressful experience for future adaptive behavior. It is also suggested that mesocortical dopamine plays an important adaptive role in this region by preventing excessive behavioral and physiological stress reactivity. The rat brain shows substantial hemispheric specialization in many respects, and while the right PFC is normally dominant in the activation of stress-related systems, the left may play a role in countering this activation through processes of interhemispheric inhibition. This proposed basic template for the lateralization of stress regulatory systems is suggested to be associated with efficient stress and emotional self-regulation, and also to be shaped by both early postnatal experience and gender differences.

Nutrient intake in women with primary and secondary Sjögren's syndrome.

OBJECTIVE: Recently, it has been proposed that dietary factors may contribute to the etiology and progression of Sjögren's syndrome, and that nutritional intervention may modify the severity of pathological abnormalities. The objective of this study was to determine whether the nutrient intake of women with primary (1 degrees SS) or secondary (2 degrees SS; ie with systemic lupus erythematosus (2 degrees SS/SLE) or rheumatoid arthritis (2 degrees SS/RA) Sjögren's syndrome is significantly different than that of age- and gender-matched controls. DESIGN: Women with Sjögren's syndrome were asked to complete the 97 General Purpose Semi-Quantitative Food Frequency Questionnaire, which consists of a list of 147 separate food items that represent the major sources of multiple nutrients. Nutritional data were evaluated in terms of absolute and energy-adjusted nutrient amounts and analyzed by ANOVA. RESULTS: Our results showed: (a) greater intake of energy, glutamate, carbohydrates, lactose, phosphorus, caffeine and unsupplemental thiamin and riboflavin in 1 degrees SS, as well as supplemental calcium in 2 degrees SS/SLE, compared with controls; (b) greater nutrient intake of energy, protein, glutamate, methionine, tryptophan, carbohydrates, lactose, supplemental calcium and phosphorus, sodium, caffeine and unsupplemental calcium, riboflavin and thiamin in 2 degrees SS/RA, relative to 1 degrees SS and/or 2 degrees SS/SLE; (c) higher energy-adjusted values for supplemental calcium in 2 degrees SS/SLE, and for vitamin A and supplemental iron and zinc in 2 degrees SS/RA, compared with other groups; and (d) higher energy-adjusted intake of supplemental calcium, and a lower energy-adjusted intake of unsupplemental vitamin C, polyunsaturated fat, linoleic acid, omega-3 fatty acid, and specific other unsaturated fatty acids, in the Sjögren's syndrome group as a whole, relative to controls. CONCLUSIONS: Our findings demonstrate that nutrient intake is altered in Sjögren's syndrome.

Effects of basolateral amygdala dopamine depletion on the nucleus accumbens and medial prefrontal cortical dopamine responses to stress.

In vivo voltammetry was used to study the effects of basolateral amygdala dopamine depletion on stress-induced dopamine release in the nucleus accumbens and medial prefrontal cortex. Male Long-Evans rats received bilateral microinjections of 6-hydroxydopamine or vehicle into the basolateral amygdala. Changes in dopamine signal were monitored in the nucleus accumbens and in the right and left hemispheres of medial prefrontal cortex, in lesioned animals and shams. Animals were subjected to a physical stressor (tail pinch) and a species-typical threat (fox odour); each stressor was presented twice over four consecutive daily sessions. The results indicate that the nucleus accumbens dopamine responses to both stressors are significantly potentiated by dopamine-depleting lesions to basolateral amygdala. In contrast, while the dopamine stress response in the left medial prefrontal cortex did not differ between lesioned animals and shams, the right medial prefrontal cortical dopamine response to tail pinch, but not fox odour stress, was significantly attenuated in lesioned animals. Therefore, basolateral amygdala dopamine depletion had opposite effects on the nucleus accumbens and medial prefrontal cortical dopamine responses to stress, although the effect on the latter is lateralized to the right hemisphere in a stressor-specific manner. These data indicate that stress-induced activation of meso-amygdaloid dopamine exerts an inhibitory influence on the nucleus accumbens dopamine response to stress. They also suggest the possibility that meso-amygdaloid dopamine influences the nucleus accumbens dopamine response to stress indirectly by modulating stress-induced dopamine release in medial prefrontal cortex. These findings add to a growing body of evidence of a preferential involvement of right medial prefrontal cortical dopamine in a wide range of physiological responses to stress.