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Biomedical subjects

Klaus Lieb

Publications and source records attributed to Klaus Lieb.

At least 37 records · Page 2Linked to original sources
PubMed2005

Effects of substance P and its antagonist L-733060 on long term potentiation in guinea pig hippocampal slices.

The neuropeptide substance P (SP) has been suggested to be involved in several physiological and pathological conditions including learning and memory and the processing of pain. This study investigated for the first time acute effects of SP and the neurokinin-1 (NK-1) receptor antagonist L-733060 on long term potentiation (LTP) in the hippocampus. Electrically evoked fEPSP was tested under the influence of SP in the CA1 region of the guinea pig hippocampus. Concentrations of 1 and 10 microM SP increased fEPSP slopes to 114.3+/-4.5% and 115.8+/-2.7%, respectively. A threshold concentration was found at 0.1 microM SP. The SP-specific NK-1 receptor antagonist L-733060 did not influence fEPSP in a concentration of 1 microM. In experiments with LTP, a significant increase of potentiations after 60 min was seen with 1 microM SP. Even if the initial baseline increase due to SP (1 microM) was subtracted, potentiations were bigger compared to controls. L-733060 (1 microM) suppressed the excitatory effects of 1 microM SP nearly complete and subsequent induced LTP was not increased. In conclusion, SP has excitatory effects in the hippocampus and is able to facilitate LTP via activation of the NK-1 receptor.

Animals↗
PubMed2005

Affective dysregulation and dissociative experience in female patients with borderline personality disorder: a startle response study.

Affective dysregulation and dissociation are currently discussed as core features of borderline personality disorder (BPD). Affective dysregulation is hypothesized to be correlated with increased amygdala functioning and dissociation is linked to inhibited processing on the amygdala and dampened autonomic output, according to the corticolimbic disconnection model of dissociation from Sierra and Berrios [Biological Psychiatry 44 (1998) 898]. We assessed startle response, which is mainly mediated by the amygdala, to investigate the relationship between affective dysregulation and dissociation. We hypothesized that patients with BPD would reveal enhanced responses to startling tones, but that these would be lessened by the presence of state dissociative experiences. 21 unmedicated female patients with BPD and 21 healthy female controls listened to 15 startling tones (95-dB, 500-ms, 1000-Hz) while heart rate, skin conductance and orbicularis oculi electromyogram responses were measured. Covariance analysis showed that the BPD group had a significantly higher startle response in the electromyogram as compared to controls. Furthermore, present-state dissociative experiences significantly influenced the startle response. Patients with low dissociative experiences revealed enhanced startle responses whereas patients with high dissociative experiences showed reduced responses. Our data support affective dysregulation in BPD as well as the corticolimbic disconnection model of dissociation, at least for EMG. Furthermore, it highlights the importance of assessing present-state dissociation in basic research as well as psychotherapy.

Adult↗
PubMed2005

Sleep in adults with attention-deficit/hyperactivity disorder: a controlled polysomnographic study including spectral analysis of the sleep EEG.

STUDY OBJECTIVES: Previous studies in children with attention-deficit/hyperactivity disorder and attention deficit disorder (ADHD/ADD) have shown impaired sleep quality with increased nocturnal motor activity. However, polysomnographic findings are not unequivocal. Up to now, in adults with ADHD, only 1 case-control polysomnographic study with small sample size has been performed. We investigated objective and subjective sleep quality in adultADHD, including an electroencephalogram spectral power analysis. DESIGN: Single-blind comparative study. SETTING: University medical center. PARTICIPANTS: Twenty adult unmedicated ADHD patients without current comorbid major depression, drug abuse, or comorbid axis-II disorder and 20 sex- and age-matched control subjects. INTERVENTIONS: N/A. MEASUREMENTS: Conventional polysomnographic parameters and sleep electroencephalogram spectral power analysis was calculated for the 2 laboratory nights. Subjective sleep parameters were estimated by sleep questionnaires to assess the relationship between objective and subjective sleep measurements. RESULTS: Adult ADHD patients showed increased nocturnal motor activity (as indicated by heightened indexes of periodic leg movements in sleep), which was significantly inversely correlated with subjective total sleep time. Although ADHD patients displayed significantly increased objective total sleep time, the subjective ratings documented impaired sleep quality in those with ADHD. Other polysomnographic sleep patterns and spectral electroencephalogram parameters did not differ between ADHD patients and normal controls. CONCLUSIONS: Similar to children, adults with ADHD show increased nocturnal motor activity. Otherwise, sleep does not seem to be impaired in ADHD patients. However, the dissociation between objective and subjective sleep parameters points to a misinterpretation of sleep quality in patients with ADHD.

Adult↗
PubMed2005

Serotonin via 5-HT7 receptors activates p38 mitogen-activated protein kinase and protein kinase C epsilon resulting in interleukin-6 synthesis in human U373 MG astrocytoma cells.

Serotonin [5-hydroxytryptamine (5-HT)] is a widely distributed neurotransmitter which is involved in neuroimmunomodulatory processes. Previously, it has been demonstrated that 5-HT may induce interleukin (IL)-6 expression in primary rat hippocampal astrocytes. The present study was undertaken to investigate the molecular pathways underlying this induction of IL-6 synthesis. As a model system, we used the human astrocytoma cell line U373 MG, which synthesizes IL-6 upon stimulation with various inducers. 5-HT dose- and time-dependently induced IL-6 protein synthesis. We identified several 5-HT receptors to be expressed on U373 MG cells, including the 5-HT1D, 5-HT2A, 5-HT3 and 5-HT7 receptors. In this report, we show that the 5-HT-induced IL-6 release is mediated by the 5-HT7 receptor based on several agonist/antagonists that were used. 5-HT-induced IL-6 synthesis is inhibited by the partially selective 5-HT7 receptor antagonist, pimozide, and the selective antagonist SB269970. Furthermore, IL-6 synthesis was induced by the 5-HT7 receptor agonist carboxamidotryptamin. In addition, we found p38 MAPKs and protein kinase C (PKC) epsilon to be involved in 5-HT-induced IL-6 synthesis as specific inhibitors of these enzymes (SB202190 and RO-31-8425, respectively) blocked 5-HT-induced IL-6 synthesis. Furthermore, 5-HT mediated the phosphorylation of both p38 MAPK as well as the PKC epsilon isoform. The p42/44 MAPKs, however, were not involved in 5-HT-induced IL-6 synthesis. This study shows, for the first time, a central role of 5-HT7 receptor linked to p38 MAPK and PKC epsilon for the induction of cytokine synthesis in astrocytic cells.

Astrocytoma↗
PubMed2005

Substance P receptor antagonists in psychiatry: rationale for development and therapeutic potential.

Increasing evidence suggests that substance P (SP) and its receptor (neurokinin [NK]-1 receptor [NK1R]) might play an important role in the modulation of stress-related, affective and/or anxious behaviour. First, SP and NK1R are expressed in brain regions that are involved in stress, fear and affective response (e.g. amygdala, hippocampus, hypothalamus and frontal cortex). Second, the SP content in these areas changes upon application of stressful stimuli. Third, the central administration of SP produces a range of fear-related behaviours. In addition, the SP/NK1R system shows significant spatial overlap with neurotransmitters such as serotonin and noradrenaline (norepinephrine), which are known to be involved in the regulation of stress, mood and anxiety. Therefore, it was hypothesised that blockade of the NK1R might have anxiolytic as well as antidepressant effects. Preclinical studies investigating the effects of genetic or pharmacological NK1R inactivation on animal behaviour in assays relevant to depression and anxiety revealed that the behavioural changes resemble those seen with reference antidepressant or anxiolytic drugs. Furthermore, antagonism or genetic inactivation of the NK1R causes alterations in serotonin and norepinephrine neuronal transmission that are likely to contribute to the antidepressant/anxiolytic activity of NK1R antagonists but that are--at least partially--distinct from those produced by established antidepressant drugs. This underlines the conceivable unique mechanism of action of this new class of compounds. In three independent clinical trials with three different compounds (aprepitant [MK-869], L-759274 and CP-122721), an antidepressant effect of NK1R antagonists could be demonstrated. These results, however, have been challenged by recent failed studies with aprepitant. There are numerous indications from preclinical studies that, in addition to SP and NK1R, other neurokinins and/or neurokinin receptors might also be involved in the modulation of stress-related behaviour and that exclusive blockade of the NK1R might not be sufficient to produce consistent anxiolytic and antidepressant effects. One such candidate is the neurokinin-2 receptor (NK2R), and clinical trials to assess the antidepressant effects of NK2R antagonists are currently underway. Of special interest might also be substances that block more than one receptor type such as NK1/2R antagonists or NK1/2/3R antagonists. These compounds may be more efficacious in antagonising the effects of SP than compounds that only block the NK1R.

Animals↗
PubMed2004

New developments in the neurobiology of borderline personality disorder.

Within the past several years, research on the clinical phenomena and neurobiology of borderline personality disorder has increased substantially. Borderline personality disorder is currently best thought of in terms of dimensions rather than as a categorical disorder. This article reviews the most recent findings on two of the core dimensions--affective dysregulation and impulsivity. Most of the neuropsychologic, physiologic, endocrinologic, and neuroimaging data support the theory that a dual brain pathology, affecting prefrontal and limbic circuits, may underlie this hyperarousal-dyscontrol syndrome.

Borderline Personality Disorder↗
PubMed2004

Differential nociceptive deficits in patients with borderline personality disorder and self-injurious behavior: laser-evoked potentials, spatial discrimination of noxious stimuli, and pain ratings.

Approximately 70-80% of women meeting criteria for borderline personality disorder (BPD) report attenuated pain perception or analgesia during non-suicidal, intentional self-mutilation. The aim of this study was to use laser-evoked potentials (LEPs) and psychophysical methods to differentiate the factors that may underlie this analgesic state. Ten unmedicated female patients with BPD (according to DSM-IV) and 14 healthy female control subjects were investigated using brief radiant heat pulses generated by a thulium laser and five-channel LEP recording. Heat pulses were applied as part of a spatial discrimination task (two levels of difficulty) and during a mental arithmetic task. BPD patients had significantly higher heat pain thresholds (23%) and lower pain ratings (67%) than control subjects. Nevertheless, LEP amplitudes were either normal (N1, P2, P3) or moderately enhanced in BPD patients (N2). LEP latencies and task performance did not differ between patients and control subjects. The P3 amplitudes, the vertex potential (N2-P2), and the N1, which is generated near the secondary somatosensory cortex, were significantly reduced during distraction by mental arithmetic in both groups. In addition, P3 amplitudes reflected task difficulty. This study confirms previous findings of attenuated pain perception in BPD. Normal nociceptive discrimination task performance, normal LEPs, and normal P3 potentials indicate that this attenuation is neither related to a general impairment of the sensory-discriminative component of pain, nor to hyperactive descending inhibition, nor to attention deficits. These findings suggest that hypoalgesia in BPD may primarily be due to altered intracortical processing similar to certain meditative states.

Adult↗
PubMed2004

Effectiveness of inpatient dialectical behavioral therapy for borderline personality disorder: a controlled trial.

Dialectical Behavioral Therapy (DBT) was initially developed and evaluated as an outpatient treatment program for chronically suicidal individuals meeting criteria for borderline personality disorder (BPD). Within the last few years, several adaptations to specific settings have been developed. This study aims to evaluate a three-month DBT inpatient treatment program. Clinical outcomes, including changes on measures of psychopathology and frequency of self-mutilating acts, were assessed for 50 female patients meeting criteria for BPD. Thirty-one patients had participated in a DBT inpatient program, and 19 patients had been placed on a waiting list and received treatment as usual in the community. Post-testing was conducted four months after the initial assessment (i.e. four weeks after discharge for the DBT group). Pre-post-comparison showed significant changes for the DBT group on 10 of 11 psychopathological variables and significant reductions in self-injurious behavior. The waiting list group did not show any significant changes at the four-months point. The DBT group improved significantly more than participants on the waiting list on seven of the nine variables analyzed, including depression, anxiety, interpersonal functioning, social adjustment, global psychopathology and self-mutilation. Analyses based on Jacobson's criteria for clinically relevant change indicated that 42% of those receiving DBT had clinically recovered on a general measure of psychopathology. The data suggest that three months of inpatient DBT treatment is significantly superior to non-specific outpatient treatment. Within a relatively short time frame, improvement was found across a broad range of psychopathological features. Stability of the recovery after one month following discharge, however, was not evaluated and requires further study.

Adolescent↗
PubMed2004

1-trichloromethyl-1,2,3,4-tetrahydro-beta-carboline-induced apoptosis in the human neuroblastoma cell line SK-N-SH.

Trichloroethylene, a common industrial solvent and a metabolic precursor of chloral hydrate, occurs widely in the environment. Chloral hydrate, which is also used as a hypnotic, has been found to condense spontaneously with tryptamine, in vivo, to give rise to a highly unpolar 1-trichloromethyl-1,2,3,4-tetrahydro-beta-carboline (TaClo) that has a structural analogy to the dopaminergic neurotoxin N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Earlier studies have revealed the relative permeability of the molecule through the blood-brain barrier and its ability to induce Parkinson-like symptoms in rats. In this study, we report that TaClo induces an apoptotic pathway in the human neuroblastoma cell line, SK-N-SH, involving the translocation of mitochondrial cytochrome c to the cytosol and activation of caspase 3. TaClo-induced apoptosis shows considerable differences from that mediated by other Parkinson-inducing agents such as MPTP, rotenone and manganese. Although it is not clear if the clinically administered dosage of chloral hydrate or the relatively high environmental levels of trichloroethylene could lead to an onset of Parkinson's disease, the spontaneous in vivo formation of TaClo and its pro-apoptotic properties, as shown in this report, should be considered.

Apoptosis↗
PubMed2004

Clonidine in acute aversive inner tension and self-injurious behavior in female patients with borderline personality disorder.

BACKGROUND: States of strong aversive inner tension and dissociative symptoms are clinical hallmarks of borderline personality disorder and major reasons for self-injurious behavior, a severe clinical condition for which there are no established pharmacologic treatment options. METHOD: The acute effect of 75 and 150 microg of clonidine administered orally in acute states of strong aversive inner tension and urge to commit self-injurious behavior was examined in 14 female patients meeting DSM-IV criteria for borderline personality disorder. Before and 30, 60, and 120 minutes after administration of clonidine, aversive inner tension and dissociative symptoms were assessed using a self-rating instrument for aversive inner tension and dissociation (Dissociation-Tension-Scale acute), and the urge to commit self-injurious behavior and suicidal ideations were assessed using self-rating Likert scales. Blood pressure and heart rate were monitored during the trial. RESULTS: Aversive inner tension and urge to commit self-injurious behavior before administration of clonidine were strong. After administration of clonidine in both doses, aversive inner tension, dissociative symptoms, urge to commit self-injurious behavior, and suicidal ideations significantly decreased. The strongest effects were seen between 30 and 60 minutes after drug intake and correspond to the pharmacokinetics of clonidine with maximum plasma concentrations after 1 hour. Blood pressure and aversive inner tension and dissociative symptoms were positively correlated before and after administration of clonidine. CONCLUSION: Orally given clonidine may be effective for treatment of acute states of aversive inner tension, dissociative symptoms, and urge to commit self-injurious behavior in female patients with borderline personality disorder. Further placebo-controlled studies with larger populations are needed to confirm this finding.

Acute Disease↗
PubMed2003

Frontolimbic brain abnormalities in patients with borderline personality disorder: a volumetric magnetic resonance imaging study.

BACKGROUND: Dual frontolimbic brain pathology has been suggested as a possible correlate of impulsivity and aggressive behavior. One previous study reported volume loss of the hippocampus and the amygdala in patients with borderline personality disorder. We measured limbic and prefrontal brain volumes to test the hypothesis that frontolimbic brain pathology might be associated with borderline personality disorder. METHODS: Eight unmedicated female patients with borderline personality disorder and eight matched healthy controls were studied. The volumes of the hippocampus, amygdala, and orbitofrontal, dorsolateral prefrontal, and anterior cingulate cortex were measured in the patients using magnetic resonance imaging volumetry and compared to those obtained in the controls. RESULTS: We found a significant reduction of hippocampal and amygdala volumes in borderline personality disorder. There was a significant 24% reduction of the left orbitofrontal and a 26% reduction of the right anterior cingulate cortex in borderline personality disorder. Only left orbitofrontal volumes correlated significantly with amygdala volumes. CONCLUSIONS: While volume loss of a single brain structure like the hippocampus is quite an unspecific finding in neuropsychiatry, the patterns of volume loss of the amygdala, hippocampus, and left orbitofrontal and right anterior cingulate cortex might differentiate borderline personality disorder from other neuropsychiatric conditions.

Adult↗
PubMed2003

Inhibition of LPS-induced iNOS and NO synthesis in primary rat microglial cells.

Nitric oxide (NO) has been implicated in the etiopathology of multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE), and inhibition of NO synthesis has been proposed to be a possible mechanism of action of drugs to treat MS. In the present study, we investigated the inhibitory effect on NO synthesis of various steroids, cytokines and drugs used or proposed for the treatment of MS. As a model system, we used primary rat microglial cells which produce NO synthase and subsequently release NO upon stimulation with lipopolysaccharide (LPS). Among the substances tested, the glucocorticoids prednisone, hydrocortisone, dexamethasone and progesterone as well as transforming growth factor-beta (TGF-beta) dose-dependently inhibited LPS-induced nitric oxide synthase (iNOS) and NO synthesis. In contrast, COP-1, the phosphodiesterase inhibitors rolipram and pentoxifylline, the cytokines interleukin-10 (IL-10) and interferon-beta (IFN-beta) as well as the steroids beta-estradiol, testosterone, and dehydroepiandrosterone (DHEA) showed no inhibitory effect. Cholesterol slightly, but not significantly, increased LPS-induced nitric oxide synthesis. We conclude from the present study that with respect to treatment of MS, inhibition of NO synthesis may be an important mechanism of action of glucocorticoids and transforming growth factor-beta, but not of other drugs used or proposed to treat MS.

Algorithms↗
PubMed2003

Valproic acid inhibits substance P-induced activation of protein kinase C epsilon and expression of the substance P receptor.

The neuropeptide substance P (SP) has been hypothesized to be involved in the etiopathology of affective disorders. This hypothesis is based on the findings that neurokinin-1-receptor antagonists have antidepressant effects in depressed patients and that SP may worsen mood. In this study, we investigated the effect of the mood-stabilizing agents valproic acid (VPA), carbamazepine, and lithium on SP-induced gene expression. As a model system, we used primary rat astrocytes and human astrocytoma cells, which both express functional SP-receptors and, upon stimulation with SP, synthesize interleukin-6 (IL-6), a cytokine which has been shown to be elevated during the acute depressive state. We found that VPA dose-dependently inhibited SP-induced IL-6 synthesis which was seen with pre-incubation periods of 30 min, 3, 7 and 14 days, whereas carbamazepine and lithium showed no inhibitory effect. The inhibitory effect of VPA was not mediated by inhibition of the stress-regulated kinases p38 and p42/44 (Erk1/2) but by inhibition of protein kinase C epsilon activation. Furthermore, VPA down-regulated the expression of the substance P receptor (neurokinin(NK)-1-receptor) as assessed by real-time PCR. Whether both mechanisms contribute to the mood-stabilizing properties of VPA has to be evaluated in further studies.

Animals↗
PubMed2003

Synergistic inhibitory effect of ascorbic acid and acetylsalicylic acid on prostaglandin E2 release in primary rat microglia.

Ascorbic acid (vitamin C) has been suggested to protect cerebral tissue in a variety of pathophysiological situations such as head trauma, ischemia or Alzheimer's disease. Most of these protective actions have been attributed to the antioxidative capacity of ascorbic acid. Besides the presence of elevated levels of oxygen radicals, prostaglandins produced by neurones and microglial cells seem to play an important role in prolonged tissue damage. We investigated whether ascorbic acid alone inhibits prostaglandin E2 (PGE2) synthesis and may augment the inhibitory effect of acetylsalicylic acid on prostaglandin synthesis. Ascorbic acid dose-dependently inhibited PGE2 synthesis in lipopolysaccharide-treated primary rat microglial cells (IC50 = 3.70 micro m). In combination with acetylsalicylic acid (IC50 = 1.85 micro m), ascorbic acid augmented the inhibitory effect of acetylsalicylic acid on PGE2 synthesis (IC50 = 0.25 micro m in combination with 100 micro m ascorbic acid). Ascorbic acid alone or in combination with acetylsalicylic acid did not inhibit cyclooxygenase-2 (COX-2) protein synthesis but inhibited COX-2 enzyme activity. Our results show that ascorbic acid and acetylsalicylic acid act synergistically in inhibiting PGE2 synthesis, which may help to explain a possible protective effect of ascorbic acid in various brain diseases.

Animals↗
PubMed2003

Neurokinin-1 receptor expression and its potential effects on tumor growth in human pancreatic cancer.

The neurokinin-1 receptor (NK-1R) and its ligand substance P (SP) are involved in the pathogenesis of certain neural tumors. Because nerves are significantly altered in pancreatic cancer, evidence for alteration of this pathway in human pancreatic cancer was sought. Expression of NK-1R was analyzed by real-time quantitative RT-PCR, in situ hybridization, immunohistochemistry, and Western blot analysis in normal human pancreatic and pancreatic cancer tissue samples and in pancreatic cancer cell lines. Furthermore, the influence of SP analogs and of the NK-1R antagonist MEN 11467 on pancreatic cancer cell growth was analyzed by sulforhodamine B (SRB) assay. By real-time quantitative RT-PCR, NK-1R mRNA was increased 36.7-fold (p < 0.001) in human pancreatic cancer samples compared with normal controls. Enhanced NK-1R expression levels were not related to tumor grade but were associated with advanced tumor stage and poorer prognosis. By in situ hybridization and immunohistochemistry, NK-1R mRNA and immunoreactivity were only occasionally weakly present in acinar and ductal cells in the normal pancreas. In contrast, moderate to strong NK-1R mRNA signals and immunoreactivity were present in most cancer cells. By Western blot analysis, NK-1R was increased 26-fold (p < 0.01) in pancreatic cancer samples in comparison to normal controls. NK-1R mRNA was detected in five pancreatic cancer cell lines by real-time quantitative RT-PCR, with the highest levels in CAPAN-1 cells and the lowest in ASPC-1 cells. SP analogs stimulated pancreatic cancer cell growth, depending on the NK-1R expression level, and this effect could be blocked by a selective NK-1R antagonist. These findings illustrate that the NK-1R pathway is activated in human pancreatic cancer and has the potential to contribute to cancer cell growth, thus suggesting the existence of a neuro-cancer cell interaction in vivo.

Blotting, Western↗
PubMed2003

Subtype differentiation of patients with borderline personality disorder using a circumplex model of interpersonal behavior.

The considerable heterogeneity of symptomatology in persons with borderline personality disorder (BPD) has led some to suggest the existence of subtypes within this diagnosis. However, no study to date has examined subtypes according to differences in interpersonal functioning, despite the central role of interpersonal problems in the BPD diagnosis. The interpersonal problems of 95 patients with BPD were investigated using the German version of the Inventory of Interpersonal Problems, a self-report measure based on a circumplex model of interpersonal functioning. Data were analyzed by means of cluster analysis. The results supported the existence of two distinct subtypes of persons with BPD, labeled "autonomous" and "dependent." Four-month longitudinal assessment indicated that these types were stable over time, suggesting the categorization reflected trait, as opposed to state, patterns of interpersonal behavior. Implications of these findings for future research and management of BPD are discussed.

Adolescent↗
PubMed2003

Substance P and Substance P receptor antagonists in the pathogenesis and treatment of affective disorders.

Substance P (SP) is a neuropeptide which is widely distributed in the periphery and the central nervous system (CNS), where it is co-localised with other neurotransmitters such as serotonin or dopamine and where it acts as a neuromodulator. SP has been proposed to play a role in the aetiopathology of asthma, inflammatory bowel disease, emesis, psoriasis, as well as neuropsychiatric disorders including pain syndromes (e.g. migraine and fibromyalgia) and affective disorders, anxiety disorders, schizophrenia and Alzheimer's disease. This review focuses on the role of SP in the pathogenesis of affective disorders. It summarises the current knowledge on measurements of SP in the CSF and serum in patients with depressive disorders or fibromyalgia, effects of SP-application in humans, SP-receptor expression in postmortem brains and the modulation of SP levels in the course of antidepressant treatment. It also discusses the promise of substance P-receptor antagonists (SPA) for the treatment of affective disorders and their proposed mechanism of action. In summary, much more research is needed to elucidate the role of SP in the pathogenesis of depression. SPA are promising as future drugs for the treatment of affective disorders, but current clinical trials have yet to be completed to draw a firm conclusion. Key words: substance P, neurokinin1-receptor, affective disorders, depression, review.

Animals↗