Pathophysiology Of Anxiety Research Articles

Gender-Specific Association of Galanin Polymorphisms with HPA-Axis Dysregulation, Symptom Severity, and Antidepressant Treatment Response

Galanin (GAL) is an estrogen-inducible neuropeptide, highly expressed in brain regions reported to be involved in regulation of mood and anxiety. GAL possibly has a direct modulatory effect on hypothalamic-pituitary-adrenal (HPA)-axis regulation. Recent data from pharmacological and genetic studies indicate a significant function of GAL in stress-related disorders. By using a tag SNP approach covering the locus encoding preprogalanin (PPGAL), earlier findings of female-specific associations of polymorphisms in this locus with panic disorder were expanded to a larger sample of 268 outpatients with anxiety disorders (ADs). Within a larger sample of 541 inpatients with major depressive disorder (MDD), we then tested associations of one PPGAL tag SNP with specific depression symptom clusters and HPA-axis activity assessed by the combined dexamethasone-suppression/CRH-stimulation test both at inpatient admission and discharge (n=298). Gender specificity as well as dependence of the association on levels of circulating estrogens was analyzed. Genotyping revealed high linkage disequilibrium in the promoter area of the PPGAL gene, which includes several estrogen-response elements. Confirming earlier results, rs948854, tagging this promoter region, was associated with more severe anxiety pathology in female AD patients, but not in males. In premenopausal female MDD patients, the same allele of rs948854 was associated with more severe vegetative but not cognitive depressive symptoms at discharge and worse treatment response on antidepressant medication. Furthermore, this allele was associated with higher HPA-axis activity at admission. No significant case-control associations could be observed. However, because of power limitations of both patient samples, small effects cannot be excluded. The reported associations in independent samples of AD and MDD support an estrogen-dependent function of GAL in pathophysiology of anxiety and depression, affecting response to antidepressant treatment.

PW01-45 - Biomarker discovery for psychiatric disorders by stable isotope metabolic labeling and quantitative proteomics

ObjectivesBiomarkers for psychiatric disorders are critical for patient stratification, premorbid diagnosis and personalized treatment. Our aim is to identify protein biomarkers for anxiety disorders by comparing the synaptic proteomes of a well-established mouse model of high (HAB), normal (NAB) and low (LAB) anxiety-related behavior.MethodsWe have compared protein expression levels using 15N metabolic labeling and quantitative proteomics. Mice were metabolically labeled through feeding with a 15N-enriched diet. Synaptosomes from unlabeled HAB and LAB mice were then compared with synaptosomes from 15N labeled NAB mice by quantitative mass spectrometry. Protein expression differences were validated with Western blots, enzymatic assays and in silico pathway analysis.ResultsWe have identified numerous protein expression differences between HAB and LAB synaptosome proteomes. We observed alterations in energy metabolism pathways such as the Krebs cycle as well as in mitochondrial function. Furthermore, we detected changes in transport and phosphorylation processes.ConclusionsWe present an accurate proteomics platform for biomarker discovery in psychiatric disorders. We identified candidate biomarkers and pathways involved in anxiety pathophysiology. Our data provide the basis for the establishment of a biomarker panel that will shed light on anxiety pathophysiology and can be applied for optimal therapeutic intervention.

Antidepressant- and anxiolytic-like properties of dopamine receptor agonist cabergoline

Non-motor symptoms of Parkinson's disease are under-studied and therefore not well treated. Here, we investigated the role of combined depletions of dopamine, norepinephrine and/or serotonin in the manifestation of motor and non-motor deficits in the rat. Then, we studied the impact of these depletions on the efficacy of deep brain stimulation of the subthalamic nucleus (STN–DBS). We performed selective depletions of dopamine, norepinephrine and serotonin, and the behavioral effects of different combined depletions were investigated using the open field, the elevated plus maze and the forced swim test. Bilateral dopamine depletion alone induced locomotor deficits associated with anxiety and mild “depressive-like” behaviors. Although additional depletions of norepinephrine and/or serotonin did not potentiate locomotor and anxiety disorders, combined depletions of the three monoamines dramatically exacerbated “depressive-like” behavior. STN–DBS markedly reversed locomotor deficits and anxiety behavior in animals with bilateral dopamine depletion alone. However, these improvements were reduced or lost by the additional depletion of norepinephrine and/or serotonin, indicating that the depletion of these monoamines may interfere with the antiparkinsonian efficacy of STN–DBS. Furthermore, our results showed that acute STN–DBS improved “depressive-like” disorder in animals with bilateral depletion of dopamine and also in animals with combined depletions of the three monoamines, which induced severe immobility in the forced swim test. Our data highlight the key role of monoamine depletions in the pathophysiology of anxiety and depressive-like disorders and provide the first evidence of their negative consequences on the efficacy of STN–DBS upon the motor and anxiety disorders in the context of Parkinson's disease.

The CRF system, stress, depression and anxiety-insights from human genetic studies.

A concatenation of findings from preclinical and clinical studies support a preeminent function for the corticotropin-releasing factor (CRF) system in mediating the physiological response to external stressors and in the pathophysiology of anxiety and depression. Recently, human genetic studies have provided considerable support to several long-standing hypotheses of mood and anxiety disorders, including the CRF hypothesis. These data, reviewed in this report, are congruent with the hypothesis that this system is of paramount importance in mediating stress-related psychopathology. More specifically, variants in the gene encoding the CRF(1) receptor interact with adverse environmental factors to predict risk for stress-related psychiatric disorders. In-depth characterization of these variants will likely be important in furthering our understanding of the long-term consequences of adverse experience.

Brain Norepinephrine System as a Target for Antidepressant and Mood Stabilizing Medications

There are numerous lines of evidence pointing to norepinephrine being of crucial importance in pathophysiology of anxiety and mood disorders. First, norepinephrine projections innervate the limbic system, suggesting the involvement of norepinephrine in the regulation of emotions and cognition. Second, norepinephrine closely interacts with serotonin and dopamine systems, which also play very important roles in the regulation of mood. Third, it has been shown that various agents which increase norepinephrine availability, such as norepinephrine reuptake inhibitors, are also effective antidepressant drugs. And fourth, the depletion of norepinephrine causes a resurgence of depressive symptoms after successful treatment with antidepressant drugs. These observations suggest that the intensification of norepinephrine transmission can be beneficial in the treatment of affective disorders. However, various psychotropic medications have indirect effect on norepinephrine transmission. This review examines the effects of psychiatric medications on the norepinephrine system and proposes how they might be used to improve treatment outcome.

Anxiety, Depression, and Quality of Life in Parkinson's Disease

Anxiety, Depression, and Quality of Life in Parkinson's Disease

Chronic psychosocial stress alters NPY system: Different effects in rat and tree shrew

The neuropeptide Y (NPY) system has been largely studied in relation to affective disorders, in particular for its role in the mechanisms regulating the pathophysiology of anxiety and depression and in the stress-related behaviours. Although NPY has been previously investigated in a variety of animal models of mood disorders, the receptor subtype mainly involved in the modulation of the stress response has not been identified. In the present study, the chronic psychosocial stress based on the resident-intruder protocol-an ethologically relevant paradigm known to induce behavioural and endocrine modifications which mimic depression-like symptoms-was used. Two different species were investigated: rat and tree shrew (Tupaia belangeri); the latter is regarded as an intermediate between insectivores and primates and it was chosen in this study for its pronounced territoriality. In these animals, the regulation of NPY and of Y(1), Y(2) and Y(5) receptors mRNA expression was evaluated after chronic stress and chronic antidepressant treatment by in situ hybridization in selected brain regions known to be involved in the pathophysiology of mood disorders. The animals were exposed to psychosocial stress for 35 days and concomitant daily fluoxetine treatment (10 mg/kg for rats and 15 mg/kg for tree shrews) after the first week of stress. The results confirmed a major role for hippocampal and hypothalamic NPY system in the pathophysiology of mood disorders. Although there were no evident differences between rat and tree shrew in the NPY system distribution, an opposite effect of chronic psychosocial stress was observed in the two species. Moreover, chronic antidepressant treatment was able to counteract the effects of stress and restored basal expression levels, suggesting the utility of these paradigms as preclinical models of stress-induced depression. Overall, although evident species differences were found in response to chronic psychosocial stress, the present study suggests a role for NPY receptors in the stress response and in the action of antidepressant drugs, providing further support for an involvement of this neuropeptidergic system in the pathophysiology of depression and anxiety.

Cannabis and anxiety: a critical review of the evidence

Anxiety reactions and panic attacks are the acute symptoms most frequently associated with cannabis use. Understanding the relationship between cannabis and anxiety may clarify the mechanism of action of cannabis and the pathophysiology of anxiety. Aims of the present study were to review the nature of the relationship between cannabis use and anxiety, as well as the possible clinical, diagnostic and causal implications. Systematic review of the Medline, PsycLIT and EMBASE literature. Frequent cannabis users consistently have a high prevalence of anxiety disorders and patients with anxiety disorders have relatively high rates of cannabis use. However, it is unclear if cannabis use increases the risk of developing long-lasting anxiety disorders. Many hypotheses have been proposed in an attempt to explain these relationships, including neurobiological, environmental and social influences. The precise relationship between cannabis use and anxiety has yet to be established. Research is needed to fully clarify the mechanisms of such the association.

Serotonin Transporter Availability in the Amygdala and Bed Nucleus of the Stria Terminalis Predicts Anxious Temperament and Brain Glucose Metabolic Activity

The serotonin transporter (5-HTT) plays a critical role in regulating serotonergic neurotransmission and is implicated in the pathophysiology of anxiety and affective disorders. Positron emission tomography scans using [(11)C]DASB [(11)C]-3-amino-4-(2-dimethylaminomethylphenylsulfanyl)-benzonitrile] to measure 5-HTT availability (an index of receptor density and binding) were performed in 34 rhesus monkeys in which the relationship between regional brain glucose metabolism and anxious temperament was previously established. 5-HTT availability in the amygdalohippocampal area and bed nucleus of the stria terminalis correlated positively with individual differences in a behavioral and neuroendocrine composite of anxious temperament. 5-HTT availability also correlated positively with stress-induced metabolic activity within these regions. Collectively, these findings suggest that serotonergic modulation of neuronal excitability in the neural circuitry associated with anxiety mediates the developmental risk for affect-related psychopathology.

Cardiac arrest and cardiopulmonary resuscitation dysregulates the hypothalamic-pituitary-adrenal axis.

Cardiac arrest and cardiopulmonary resuscitation (CA/CPR) increase the risk for affective disorders in human survivors. Postischemic anxiety- and depressive-like behaviors have been documented in animal models of CA/CPR; however, the stability of post-CA/CPR anxiety-like behavior over time and the underlying physiologic mechanisms remain unknown. The hypothalamic-pituitary-adrenal (HPA) axis and the corticotropin releasing factor (CRF) system may mediate the pathophysiology of anxiety and depression; therefore, this study measured CA/CPR-induced changes in CRF receptor binding and HPA axis negative feedback. Mice were exposed to CA/CPR or SHAM surgery and assessed 7 or 21 days later. Consistent with earlier demonstrations of anxiety-like behavior 7 days after CA/CPR, increased anxiety-like behavior in the open field was also present 21 days after CA/CPR. On postoperative day 7, CA/CPR was associated with an increase in basal serum corticosterone concentration relative to SHAM, but this difference resolved by postoperative day 21. The Dexamethasone Suppression Test showed that the CA/CPR group had enhanced negative feedback compared with SHAM controls at postoperative day 21. Furthermore, there was a gradual increase in CRF(1) receptor binding in the paraventricular nucleus of the hypothalamus and bed nucleus of the stria terminalis, as well as a transient decrease of both CRF(1) and CRF(2A) receptors in the dorsal hippocampus. Therefore, sustained changes in activity of the HPA axis and the CRF system after CA/CPR may contribute to the postischemic increase in affective disorders.

Long-term anxiolytic and antidepressant-like behavioural effects of tiagabine, a selective GABA transporter-1 (GAT-1) inhibitor, coincide with a decrease in HPA system activity in C57BL/6 mice

Gamma-aminobutyric acid (GABA) system plays a pivotal role in the pathophysiology of anxiety and mood disorders. This study was aimed to assess the anxiolytic and antidepressant-like properties of tiagabine, an inhibitor of the GABA transporter-1 (GAT-1), after acute and chronic administration in C57BL/6JOlaHsD mice with paroxetine as a positive control. In first experiments, the acute administration of tiagabine (7.5 mg/kg, orally [PO]) and paroxetine (10 mg/kg PO) induced anxiolytic effects in the elevated plus maze test and the modified hole board test and an antidepressant-like effect in the forced swim test. Chronic application of tiagabine (7.5 mg/kg PO) and paroxetine (10 mg/kg PO) for 22 days revealed an anxiolytic and antidepressant-like efficacy of tiagabine only. In a further experiment, we analysed the impact of chronic tiagabine versus paroxetine treatment on the hypothalamic-pituitary-adrenocortical (HPA) system regulation. GAT-1 blockade induced a setpoint-shift of the stress hormone system toward lower levels as indicated by decreased plasma corticosterone concentrations and attenuated gene expression levels of corticotropin-releasing factor in the paraventricular nucleus of the hypothalamus and of hippocampal steroid receptors. This data indicate that both acute and long-term anxiolytic and antidepressant-like properties of brain GAT-1 inhibition coincide with a reduction in HPA system activity in mice.

Sex differences in anxiety after infusion of group I mGluR agonist within the basolateral amygdala

Females are twice affected by anxiety‐related disorders than males. These differences might be due to the effects of gonadal hormones. Metabotropic glutamate receptors (mGluRs) have been implied in the pathophysiology of anxiety. We hypothesized that S‐3,5‐Dihydroxyphenylglycine (DHPG), a group I mGluRs agonist, within the basolateral amygdala (BLA) will modulate anxiety according to sex. Intact males were compared to ovariectomized female rats that contained empty implants (OVX) or implants containing estradiol (OVX‐EB). We used the Vogel Conflict Test (VCT) to analyze conflict‐based anxiety and the Cat Odor Test (COT) for innate anxiety behaviors. In the VCT, intact males displayed more punished licks than OVX female rats (p=0.05). DHPG infusion did not alter any VCT parameter in intact male, OVX and OVX‐EB female rats. In COT, intact males showed lesser number of flat back approached (FBA) and spent more time in contact with the cat odor stimuli than OVX female rats (p= 0.01 & 0.04). DHPG infusion decreased FBA (p=0.02) and stretch attended behaviors in OVX female rats only (p=0.03). In males, DHPG reduced the number of freezing behaviors (p=0.004). Our results indicate sex differences in anxiety‐related behaviors which are task‐dependent. Infusion of DHPG within BLA modulates innate anxiety behaviors in OVX female rats. We concluded that mGluRs might be a pharmacological alternative to modulate anxiety.

Current status of brain imaging in anxiety disorders

This study reviews the most recent literature about brain imaging research in anxiety disorders. There is a growing body of evidence that neuroimaging of anxiety disorders contributes to a better understanding of the neurobiology of these disorders, by identifying cerebral modifications occurring previously or subsequent to symptoms of anxiety. A systematic search of the literature (January 1978-July 2008) was performed in MEDLINE using the keywords brain imaging, anxiety disorders, posttraumatic stress disorder, obsessive-compulsive disorder, generalized anxiety disorder, specific phobia, social anxiety disorder, panic disorders and agoraphobia. References cited in all trials were searched iteratively to identify missing studies. Our review focused only on the last year's findings. There is a consensus on the crucial role of the amygdala, anterior cingulate cortex and insula in the pathophysiology of anxiety disorders. Brain imaging research in anxiety disorders has become increasingly important, especially in the last decade, because of the opportunity to validate neurobiological hypotheses for anxiety disorders. Thus, neuroimaging data raise the question of the neurobiological cause of anxiety disorders, opening up new reflections not only on pharmacological treatments but also on the nosology of the anxiety disorders.

Changes in plasma levels of BDNF and NGF reveal a gender-selective vulnerability to early adversity in rhesus macaques

Early stressful events can increase vulnerability for psychopathology, although knowledge on the effectors is still limited. Here we tested the hypothesis that peripheral levels of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF), which are involved in the response to stress and in the pathophysiology of anxiety and depression, might be affected in a non-human primate model of adverse rearing. Males and females rhesus macaques reared with their mothers (MR) or in peer-only groups (PR) were used as experimental subjects. BDNF, NGF, adrenocorticotropic hormone (ACTH), cortisol and growth hormone (GH) were determined at baseline on postnatal days (PND) 14, 30 and 60 by means of specific ELISA and RIA procedures. In addition, behavior was assessed on PND 7, 14, 21, 30 (Brazelton test) and 60 (home cage observation). Data indicate gender differences in basal levels of BDNF throughout development. Peer-rearing increased significantly BDNF levels only in females. In addition, while all peer-reared subjects showed high levels of stereotypies and self-directed behaviors, behavioral passivity was selectively increased in females. By contrast, NGF levels were increased in response to peer-rearing only in males, and correlated positively with other "classic" endocrine responses to stress, such as cortisol and GH. Our data identify BDNF and NGF as neuroendocrine markers underlying differential responses to maternal deprivation in males and females rhesus macaques. The selective changes in BDNF levels in females could help explain the greater vulnerability to mood disorders of this gender reported in humans.

Serotonin 5-HT1A receptor binding in people with panic disorder: positron emission tomography study

The importance of the neurotransmitter serotonin (5-HT) in the pathophysiology of anxiety is well known. A key role for postsynaptic 5-HT(1A) receptors has recently been suggested in studies of genetic knockout mice. To measure 5-HT(1A) receptor binding in patients with panic disorder in the untreated state and after recovery on treatment with selective serotonin reuptake inhibitors (SSRIs). Nine symptomatic untreated patients with panic disorder, seven patients recovered on SSRI medication and nineteen healthy volunteers underwent a single positron emission tomography (PET) scan using the 5-HT(1A) tracer [(11)C]WAY-100635. In comparison with controls, both presynaptic and postsynaptic 5-HT(1A) receptor binding was reduced in untreated patients, with the most significant reductions being in the raphe, orbitofrontal cortex, temporal cortex and amygdala. In recovered patients presynaptic binding was reduced, but there was no significant reduction in postsynaptic binding. Panic disorder is associated with reduced 5-HT(1A) receptor availability, which is also known to have a key role in depression.

Short-term tolerability of a nonazapirone selective serotonin 1A agonist in adults with generalized anxiety disorder: A 28-day, open-label study

Background: The serotonin 1A (5-hydroxytryptamine 1A [5-HT 1A]) receptor likely plays a critical role in anxiety pathophysiology. Objective: In this proof-of-concept investigation, we tested the short-term tolerability of PRX-00023, a nonazapirone 5-HT 1A selective partial agonist, in outpatients with generalized anxiety disorder (GAD). Methods: Patients with a diagnosis of GAD, as defined by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, and Hamilton Anxiety (HAM-A) Rating Scale scores ≥20 were recruited. A 1-week, single-blind placebo run-in was followed by a 28-day,open-label treatment with PRX-00023 QD in a forced-titration protocol: 40 mg (days 1–4), 80 mg (days 5–14), and 120 mg (days 15–28). The primary outcome measures were tolerability and rate of completion of the study. Tolerability was recorded using a table of adverse events (AEs), and measured using laboratory tests, vital signs, and electrocardiogram (ECG) readings. Secondary outcomes included the baseline—to—end point change in HAM-A total score, percentage meeting remission (HAM-A≤7), and response criteria (≥50% reduction in HAM-A total score). Results: Twenty-three patients (56.5% female, 65.2% white; mean age, 37.4 years) were enrolled in the study. A total of 21 patients (91.3%) received study medication and 18 (78.3%) completed the study. Two patients withdrew for personal reasons, 1 was discontinued for noncompliance, and 1 was lost to follow-up. One patient was discontinued from the study due to a history of premature ventricular contractions deemed unrelated to the study drug. AEs were reported in 15 patients, with the most common being back pain (3 patients), influenza-like symptoms (without fever) (2), diarrhea (2), dyspepsia (2), and nausea (2). No serious AEs, withdrawal symptoms, ataxia/ dizziness, or sexual dysfunction were reported; there were no clinically significant laboratory, vital sign, or ECG abnormalities. Mean HAM-A total scores were significantly lower at study end point compared with enrollment (13.9 vs 22.9; P < 0.001), with 32% of patients achieving remission and 52% meeting response criteria. Conclusion: In this preliminary, short-term study, PRX-00023 appeared to be generally well tolerated in this sample of patients with GAD.

Buspirone induced acute and chronic changes of neural activation in the periaqueductal gray of rats

5-HT 1A modulation within the midbrain periaqueductal gray (PAG) is closely associated with anxiety- or panic-like behavior. Several findings have demonstrated that the properties of buspirone (a 5-HT 1A partial agonist) would function as either anxiolytic or panicolytic in both clinical and laboratory animal research. In this study, we have investigated the neuronal activity occurring within the different regions of the PAG induced by buspirone treatment. Twenty-eight albino Wistar rats (350–400 g) were injected with either acute or chronic saline/buspirone (each, n=7), respectively. Our results show that buspirone treatment reduced locomotor activity, body weight and fecal boli, particularly in the chronic buspirone group. Two-way ANOVA revealed a significant decrease of c-Fos-immunoreactive (ir) cells expression in all regions of the rostral PAG after both acute and chronic buspirone (acute buspirone (AB) and chronic buspirone (CB), respectively) treatment. However, no effects on c-Fos-ir were detected in the caudal lateral periaqueductal gray (lPAG) and ventrolateral periaqueductal gray (vlPAG) in both the AB and CB groups, and in the dorsolateral periaqueductal gray (dlPAG) of the CB group. Interestingly, c-Fos-ir cells in the dorsomedial periaqueductal gray (dmPAG) column were reduced consistently in both the rostral and caudal PAG in both AB and CB groups. Besides, in all regions the number of c-Fos-ir cells was higher in the AB than in the CB group with exception of the rostral lPAG. In conclusion, the main anxiolytic effect of buspirone was specifically localized in all regions of the rostral PAG and in the caudal dmPAG. However, the caudal dlPAG, lPAG and vlPAG were found to be ineffective to buspirone treatment, probably due to their distinctive function in mediating higher level of anxiety in defensive behavior. This indicates that the longitudinal anatomical structure of the PAG possesses a different level of receptor sensitivity of 5-HT 1A in the pathophysiology of anxiety and panic disorder.

Chromosome 4q31‐34 panic disorder risk locus: Association of neuropeptide Y Y5 receptor variants

There is strong evidence for a genetic contribution to the pathogenesis of panic disorder, with a recent linkage study pointing toward a risk locus on chromosome 4q31-q34 [Kaabi et al., 2006]. Since the neuropeptide Y (NPY) system has been reported to be involved in the pathophysiology of anxiety and in particular panic disorder and the genes coding for NPY Y1, Y2, and Y5 receptors are located in the suggested risk region (4q31-q32), variants in the NPY, NPY Y1, Y2, and Y5 genes were investigated for association with panic disorder in a sample of 230 German patients with panic disorder and matched healthy controls. A synonymous (Gly-426-Gly) NPY Y5 coding variant (rs11946004) as well as haplotypes including rs11946004 and an intronic NPY Y5 variant (rs11724320) were significantly associated with panic disorder (P = 0.027), with the effect originating from the subgroup of female patients (P = 0.030), particularly with concurrent agoraphobia (P = 0.002-0.019). No association was observed for any variants located in the genes coding for NPY, NPY Y1, or Y2. The present results provide preliminary support for an influence of NPY Y5 receptor variants on the etiology of panic disorder in a potentially gender-specific manner further strengthening the evidence for a risk locus on chromosome 4q31-q34 in anxiety disorders. However, in order to allow for conclusive evaluation of the present finding and to exclude a false positive result, further studies in larger, independent, preferably family based samples are warranted.

Music exposure differentially alters the levels of brain-derived neurotrophic factor and nerve growth factor in the mouse hypothalamus

It has been reported that music may have physiological effects on blood pressure, cardiac heartbeat, respiration, and improve mood state in people affected by anxiety, depression and other psychiatric disorders. However, the physiological bases of these phenomena are not clear. Hypothalamus is a brain region involved in the regulation of body homeostasis and in the pathophysiology of anxiety and depression through the modulation of hypothalamic-pituitary-adrenal (HPA) axis. Hypothalamic functions are also influenced by the presence of the neurotrophins brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF), which are proteins involved in the growth, survival and function of neurons in the central nervous system. The aim of this study was to investigate the effect of music exposure in mice on hypothalamic levels of BDNF and NGF. We exposed young adult mice to slow rhythm music (6h per day; mild sound pressure levels, between 50 and 60 dB) for 21 consecutive days. At the end of the treatment mice were sacrificed and BDNF and NGF levels in the hypothalamus were measured by enzyme-linked immunosorbent assay (ELISA). We found that music exposure significantly enhanced BDNF levels in the hypothalamus. Furthermore, we observed that music-exposed mice had decreased NGF hypothalamic levels. Our results demonstrate that exposure to music in mice can influence neurotrophin production in the hypothalamus. Our findings also suggest that physiological effects of music might be in part mediated by modulation of neurotrophins.

Alcohol Use and Anxiety: Diagnostic and Management Issues

Alcohol Use and Anxiety: Diagnostic and Management Issues