Obsessive-compulsive disorder The serendipitous discovery that clomipramine (CMI), a more serotonergic tricyclic, is effective for obsessive-compulsive disorder (OCD) was important in giving impetus to a serotonin hypothesis of OCD.47 Subsequent work found that the more selective SSRIs were not only efficacious but also well-tolerated.48 More recent psychobiological Inhibitors,research,lifescience,medical research has focused on

delineating the role of neurotransmitters other than serotonin; dopaminergic augmentation strategies have been used clinically for some time now,49 and a range of other molecular treatment targets are being pursued.50,51 Anecdotal reports of the efficacy of CMI in OCD were followed by rigorous randomized controlled trials. Such work demonstrated Inhibitors,research,lifescience,medical that clomipramine was more efficacious than both placebo and noradrenergic tricyclic agents such as desipramine, and that it was efficacious in both adults as well as in children and adolescents with OCD.52 Such work led to the first FDA approval for OCD pharmacotherapy.15 The use of intravenous (IV) CMI for refractory OCD has also been investigated,53,54 as this route of administration avoids first-pass hepatic metabolism which breaks CMI down to its less potent form, desmethyl-clomipramine. Inhibitors,research,lifescience,medical With the introduction of the SSRIs, several studies of these

agents were undertaken in OCD, and these generally showed efficacy and safety.55 Fluoxetine, fluvoxamine, paroxetine, and sertraline have all been FDA-approved for OCD.56 While several meta-analyses have suggested that CMI may be more effective Inhibitors,research,lifescience,medical than SSRIs (Table II),57 this finding may reflect the fact that earlystudies were characterized by a lower placebo response rate. Flead-to-head comparisons of CMI and SSRIs have shown equal efficacy and superior buy MGCD0103 tolerability for the SSRIs.58 Thus, the SSRIs are now typically viewed as the first-line choice for OCD.8,9,11,56,59 Table II. Selected meta-analyses of obsessive-compulsive disorder treatment. CMI, clomipramine; SSRI, selective serotonin reuptake Inhibitors,research,lifescience,medical inhibitor;

OCD, obsessive-compulsive disorder A meta-analysis of medication dosage findings in OCD suggests that patients who fail to respond to low-dose therapy should be increased to a higher selleck chemicals llc dose.60 An adequate trial in OCD should be at least 12 weeks in length.61 Although there is less published work on the longer-term treatment of OCD, a number of studies have demonstrated that early discontinuation often leads to relapse.58 Guidelines therefore suggest that patients who respond to initial acute treatment should then be continued for at least 1 year, and withdrawn gradually.8,9,56,59 It has been suggested that efficacy can be maintained even after a reduction in dosage of long-term treatment, with the benefits of improved tolerability and adherence.

13 Maimonides was in search of the true reason for the death, as formulated in the introduction to his commentary to the Fathers’ Aphorisms (Pirqei Avot): “Accept the truth from whatever source it comes.” Maimonides moreover explained that his aim in recounting this case was to warn patients—not just physicians—to having recourse to strong drugs (such as theriac) only on the advice

of an accomplished physician, and, even then, with great caution, only in case no other treatment may be devised.14 Considering the Patient—Not Only the Disease One of the central statements of Maimonides is the following: Inhibitors,research,lifescience,medical One should never say: “This disease is similar to that [other] one.” … Nor should one say: “I have seen how my elders have treated [this disease] in such or such way.” [As a matter of fact] a physician does not treat a disease, he rather treats a sick person.15 To which he adds: “Every person who falls ill necessarily requires

renewed consideration and reflection.” Maimonides thus indicates that the Inhibitors,research,lifescience,medical constitution and the psychology of the patient must be taken into account. As stated in his Regimen Sanitatis (Heb. Hanhagat Ha-Beriut), Maimonides feels Inhibitors,research,lifescience,medical that a psychological assessment of the patient should even anticipate any medical intervention. “For every sick individual feels his/her heart constricted [Heb. libo tsar].”16 In other words, an accomplished physician should know how to adapt Inhibitors,research,lifescience,medical his way of addressing the patient according to the latter’s psychology. Psychology was then a branch of Philosophy, and we thus understand better why even Galen said that a physician should be trained in Philosophy. Establishing Authority with the Patient and His Environment In his Commentary on Hippocrates’ Aphorisms, Maimonides affirms that a physician who aims at doing his best for his Inhibitors,research,lifescience,medical patient’s benefit

must have in view more than achieving an exact diagnosis and an adequate treatment for the disease. He must care for a etc full-fledged application of the treatment. Indeed, the patient might be reluctant to take a drug that is bitter or repulsive; and the care-takers might prefer taking advice from some popular quack or from a “wise woman.”17 The physician must therefore endeavor to gain Drug_discovery full confidence from both patient and care-takers. Moreover, he should feel responsible for the removal of any impediment to the treatment; he should even help poor patients to purchase the drugs and/or to move to some healthier accommodation. The duty to help poor patients applies to every individual, including physicians, but Maimonides feels a necessity to mention it here (cf. Hilkhot ‛Aniyim 10, 4–5). According to Hippocrates, an effective way of gaining the patient’s trust is through accurate prognosis. We read: I hold that it is an excellent thing for a physician to practice Prognosis.

And 10 were misdiagnosed. The misSelleckchem MK2206 diagnosis rate was 8.53%.

The mean definite time to diagnosis was 65.3±35.0min. All 155 patients with acute chest pain in Group II, were definitely diagnosed as fatal acute chest pain. 0 was misdiagnosed. Misdiagnosis rate was 0%. The mean definite time to diagnosis was 40.1±12.7min (Table ​(Table11). Table 1 Comparison of misdiagnosis rate, definite time to diagnosis and medical expenses between the two groups Discussion Inhibitors,research,lifescience,medical Acute chest pain is a very serious emergency that threatened patient’s lives. Make a definite diagnosis as soon as possible and start certainty therapy is very critical. The main factors that delayed diagnosis and treatment of this kind of patients include insufficient cognition by oneself, time delays before visiting and diagnosis and management delayed in the hospital [3].

And the third factor is the medical part that can be improved fast as possible. In the past, the hospital pattern of diagnosis and Inhibitors,research,lifescience,medical treatment presented as assessment or previewing patients with acute chest pain by physicians depending on their personal medical expertise. This kind of pattern had multiple disadvantages. Firstly, medical resources could not be distributed effectively and reasonably. The amount of emergency patients in hospitals of class three grades A increased rapidly Inhibitors,research,lifescience,medical with the social development and the concept transition. Sometimes, there were too many patients lining up in apex time. Emergency doctors had no time to care Inhibitors,research,lifescience,medical for some patients who really needed diagnosis and cure in precedence. And acute chest pain is one of the preferential diseases. If these patients were passive and then too much time was lost

in examination for first things first, that would cause the delay of diagnosis and cure [4]. Secondly, triage of outpatients depended on the experience Inhibitors,research,lifescience,medical of charged nurse. Since her or different physicians’ experience and level were distinct, that would cause objective triage and incorrect evaluation. That resulted in failing to discover and diagnose some insidious fatal chest pain. To aim directly at the above issues, we adopted two major measures to solve them. First, all the patients complained with chest pain and chest distress were admitted to rescue room for diagnosis and cure. The consummate monitor and emergency equipments ensured the compact diagnose and examination time, which should be controlled better. And the misdiagnosis SSR128129E chemical structure rate of fatal chest pain was thus decreased [5]. Second, the procedure of diagnosis and cure was carrying out according to the acute chest pain screening flow-process diagram. This procedure avoided the experience and level difference between doctors, and the misdiagnosis rate of fatal chest pain was reduced. Through the practice of the two measures, we found the misdiagnosis rate of fatal chest pain was decreased, and the definite time to diagnosis was shortened obviously.

84 Mouse models have been very useful in delineating the relationship between disturbances to MeCP2 and the disease.85 In mice, deletion of MeCP2 mimics RTT syndrome, leading to locomotor impairments and reductions in brain size.86,87 Mice with a truncated MeCP2 protein, similar to that of RTT patients, developed many features of RTT, such as tremors, motor impairments, hypoactivity, increased anxiety-related behavior, seizures, kyphosis, and stereotypic forelimb motions; these mice

also presented hyperacetylation Inhibitors,research,lifescience,medical on histone H3,88 illustrating that chromatin abnormalities exist in this disorder. In astrocytes cultured from a mouse model of RTT, MeCP2 deficiency causes significant abnormalities in BDNF regulation, cytokine production, and neuronal dendritic induction. Whereas previous experiments have only focused on neurons, this evidence suggests that astrocytes may also represent therapeutic targets for RTT89 The classic Inhibitors,research,lifescience,medical form of autism also appears to be connected to MeCP2 expression. Coding mutations affecting the protein are rarely detected in autism, but significantly increased MeCP2 promoter methylation has been found in autistic male frontal cortex compared with controls, and this inversely correlated with protein expression90; aberrant promoter methylation

at MeCP2 has also been detected Inhibitors,research,lifescience,medical in female brain DNA.91 Similarly, loss of methyl-CpG binding protein 1 (MBD1), leads to autismlike behavioral deficits in mice, namely reduced social interaction, learning deficits, anxiety, defective Inhibitors,research,lifescience,medical sensory motor gating, depression, and abnormal brain serotonin activity.92 Also, a novel mutation has been discovered in the Jumonji AT-rich interactive domain 1C (JARID1C) gene of a child with autism. While very preliminary, this discovery is interesting, as JARID1C is believed to be a histone demethylase specific for di- and trimethylated histone 3 lysine 4 (H3K4), as well as a transcriptional repressor for the ASD-associated genes SCN2A, CACNA1H, BDNF, and SLC18A1.93 Finally, another interesting

Inhibitors,research,lifescience,medical hypothesis relating epigenetics to ASD concerns the observation that autistic children exhibit improved behavior communication during febrile episodes.94 It may be the case that fever restores the modulatory functions of the intact, LDN-193189 research buy but dysregulated locus coeruleus-noradrenergic (LC-NA) system that is present in ASD. The fact that the state of the LC-NA system can be switched back and forth, VRT752271 combined with evidence that imprinted genes within the LC-NA are tightly epigenetically regulated and susceptible to environmental interference,95 suggests that dynamic epigenetic remodeling processes may regulate the malfunctioning pathways in ASD.96 Epigenetic treatment opportunities Epigenetic drug strategies are currently employed to treat a collection of cancer subtypes, and these medications are now being considered in the treatment of psychiatric disease, as well.

Indeed, induction of tumor hypoxia and an inflammatory state caused by further information anti-angiogenic agents may promote malignancy (43,47). Other animal models, however, have shown that treatment and subsequent discontinuation of anti-VEGF therapy resulted in tumor re-growth at a slower rate than control-treated animals, speaking against a so-called rebound growth effect (18). Despite the above theoretical concerns, no clinical studies have indicated that exposure to biologic agents select for more aggressive tumors

or promote tumor invasiveness. For example, a study in patients with gliobastoma Inhibitors,research,lifescience,medical multiforme treated with the pan-VEGF Inhibitors,research,lifescience,medical receptor tyrosine kinase inhibitor, cediranib, showed no rebound angiogenesis when the drug with withheld (49). And in multiple large, randomized clinical trials with bevacizumab in multiple disease types

including renal cell carcinoma (50), breast cancer (51), and lung cancer (52), there have been no indication of re-bound tumor effect Inhibitors,research,lifescience,medical after withdrawal of bevacizumab. Conclusions New chemotherapy drug development has traditionally started with testing agents in the refractory, advanced disease setting, followed by the first line metastatic setting with only drugs with success in advanced disease advancing to testing in the adjuvant setting. However the assumption that drugs successful in macrometastatic disease will also be effective in micrometastatic disease (adjuvant setting) is Inhibitors,research,lifescience,medical increasingly being questioned, particularly in the era of biologic agents. In colon cancer, the benefit of cytotoxic agents such as 5-FU, capecitabine, and oxaliplatin did indeed translate to the adjuvant setting for most patient sub-groups. However, irinotecan showed no benefit in the adjuvant setting and bevacizumab Inhibitors,research,lifescience,medical and cetuximab even had trends towards worse outcomes when used adjuvantly. The importance of large-scale clinical trials of drugs in the exact settings in which they will be used cannot be overstated. An interesting

concern is the idea that agents unsuccessful in the metastatic setting may show efficacy in the adjuvant setting. However, acting on this possibility would involve changing the paradigm of how we currently move new drugs through clinical trials with no current examples Carfilzomib of such a drug at present. Where do we go from here in the adjuvant treatment of colon cancer and other malignancies in the biologic era? Perhaps new classes of biologic agents such as inhibitors of insulin growth factor, MEK, PI3kinase or BRAF may be more successful. Or perhaps anti-VEGF or anti-EGFR therapies have a role, but we have to identify the correct patient population, with predictive markers.

Discussion CPF predominate in adults and are particularly frequent between the 4th and 8th decades of life. Most cases are probably acquired, however the etiology is unknown.5) CPF are more frequently located on the aortic valve (40%), tricuspid valve (17%), mitral valve (14%), pulmonary valve (13%), left atrium (7%), right atrium (2%), right ventricle (2%), and left ventricle papillary muscle (1%).6) Inhibitors,research,lifescience,medical Left ventricular CPF is rare, only reported via case reports.7) Although it is found incidentally, it can result in life-threatening complications, such as coronary and cerebral embolism, acute valvular dysfunction and sudden

death.8) The most common clinical presentations are stroke, syncope, mesenteric ischemia, pulmonary emboli and sudden death.5) The clinical presentation is determined by location, size, and mobility of the tumor and when they arise from the left sided heart, systemic embolism is frequent. The treatment of choice of CPF is surgical excision, which is safe without Inhibitors,research,lifescience,medical causing significant morbidity or mortality. When valvular involvement is present, excision with valve repair or replacement is curative. Asymptomatic non-mobile or right side CPF could be Selleck NVP-BGJ398 followed-up closely.4),5) The diagnostic method of choice for CPF is TTE or transesophageal

Inhibitors,research,lifescience,medical echocardiography (TEE), although the ultimate diagnosis of CPF is based on histopathology. The most characteristic echocardiographic features that identify a tumor as a CPF are small size (usually Inhibitors,research,lifescience,medical < 1.5 cm), pedical or stalk attachment to endocardium, with high mobility, and refractive appearance and areas of echolucency within the tumor.2) Although no extensive studies have yet quantified the diagnostic

yield of TEE for CPF compared with TTE, TEE is considered to be more accurate in diagnosing CPF. For tumors with a diameter < 0.2 cm, the sensitivity of TTE was only 61.9% and of TEE was 76.6%. In contrast, the sensitivity and specificity of TTE for CPF with a diameter > 0.2 cm are 88.9% and 87.8%, respectively.9) However, it is impossible to differentiate CPF Inhibitors,research,lifescience,medical from myxomas or thrombi, using TTE or TEE alone. Magnetic resonance imaging (MRI) may be more helpful than TEE in detecting the extent of the lesion invading the myocardium. MRI typically demonstrates a CPF mass on a valve leaflet or on the endocardial surface Selleck Linifanib of the affected cardiac chamber and increase accuracy of diagnosis by showing the differential enhacement with respect to the surrounding normal cardiac structures.10) Histopathologically, CPF are composed of a central stalk with radiating villus-like projections. The papillae are avascular structures, which contains a core of dense collagen fibers admixed with varying amounts of reticulin and elastin fibers. The cells lining the elongated papillae are hyperplastic endothelial cells, occasionally bulging from the surface.11) The lining epithelium is contiguous with the rest of endocardium.

These predisposing

factors, either innate or acquired, determine individual “affective styles”2,34 or coping strategies,26 which are thought to play an important role in vulnerability to psychopathology. Animal models Some of the neurobiological mechanisms underlying anxiety may already be present in very simple organisms, such as the snail Aplysia, which can show forms of learning akin to anticipatory and chronic anxiety.35 However, most animal models of anxiety are based on the use of mammalian species, particularly rats and mice.36-42 These models fall into two broad categories. In the first one, animals are confronted Inhibitors,research,lifescience,medical with situations that generate an anxious state (state anxiety models). This state of anxiety can be either conditioned (eg, conditioned fear, avoidance, and punishment-induced conflict tests) or unconditioned (eg, aversive and ethological conflict tests). Inhibitors,research,lifescience,medical In the second category, the models are concerned with

trait or “pathological” anxiety: genetic manipulations (transgenic or “knockout” animals) or selective breeding creates lines of rats or mice that permanently express an increased or decreased level of anxiety. Functional neuroanatomy As already suspected by Letourneau Inhibitors,research,lifescience,medical and others, emotional. experience and the associated behavioral responses are likely to activate specific circuits in the brain. The search for the neuroanatomical

substrates of fear and anxiety has been a successful field of research over the last decades. For a long time, it was assumed that emotions, including fear and anxiety, were almost exclusively generated or processed in a “primitive” part of the brain, ie, the limbic Inhibitors,research,lifescience,medical system (“the emotional brain”). The view that emotions and cognitions are separate functions of the brain and must therefore have different underlying neuroanatomical substrates is probably responsible for this simplification. As pointed out by LeDoux Inhibitors,research,lifescience,medical in a recent review,43 modern research with the most advanced neuro-imaging technologies still uses this dichotomic approach to higher brain functions as a post hoc explanation: “When a so-called emotional task is used, and a limbic area is activated, the activation is explained by reference to the fact that limbic areas mediate emotions. And when a limbic area is Entinostat full report activated in a cognitive task, it is often assumed that there must have been some emotional undertone to the task.” However, neuroanatomical and behavioral data obtained during the last decades clearly indicate that this dichotomy between cognitive and emotional processes is obsolete. The locus ceruleus and arousal Autonomic activation and increased arousal are among the earlier psychophysiological responses observed in a state of fear or anxiety.

It is now clear that the neurotrophic factor-ERKl/2-MAPK-Bcl-2 signaling sellckchem cascade has a critical role in cell survival in the CNS and that a fine balance exists between the levels and activities of cell survival and cell death factors. BDNF-ERKl/2-CREB-Bcl-2 cascade dysregulation may be a key mechanism via which prolonged stress induces Inhibitors,research,lifescience,medical atrophy of select vulnerable neuronal subpopulations,

distal dendrites, or both. Although dysregulation of this cascade most likely results in decreased neuronal survival, the differential survival is likely modulated not only by region-specific expression of protective factors, but also by the network properties of vulnerable structures. Inhibitors,research,lifescience,medical Therefore, it is likely that the dynamics of the impairments

of cellular plasticity and resilience are determined by intrinsic properties of the affected regions. There is emerging evidence – mainly from postmortem studies – supporting a role for abnormalities in neurotrophic signaling pathways in depression. Decreased levels of CREB, BDNF, and the TrkB receptor have been described in suicide victims.46-48 Depressed individuals may also have genetic abnormalities in CREB and BDNF. Sequence variations in the CREB1 gene have been observed in depressed women.6 A coding variant of BDNF may be associated with the personality trait of neuroticism, Inhibitors,research,lifescience,medical which is a risk factor for depression.49 Furthermore, two recent studies50,51 suggest that a polymorphism in the pro-BDNF molecule is associated with bipolar disorder (a condition in which depressive episodes are accompanied by manic episodes). This polymorphism is associated with alterations in BDNF trafficking and secretion in vitro, as well as with alterations Inhibitors,research,lifescience,medical in hippocampal working memory

Inhibitors,research,lifescience,medical in humans.52 Therefore, an opportunity exists to study the interaction of life stress, signal transduction-related genes, neuroimaging abnormalities consistent with deficient structural plasticity, and susceptibility to depression.15 Antidepressant mechanisms and neurotrophic signaling cascades An increasing amount of evidence suggests that antidepressants regulate neurotrophic signaling cascades. Antidepressant treatment increases CREB phosphorylation and CREB-mediated Brefeldin_A gene expression in mice limbic brain regions.53 Various classes of chronic antidepressant treatments, as well as electroconvulsive treatment (ECT), upregulate CREB and BDNF expression, suggesting that the CREB cascade and BDNF are common post-receptor targets of antidepressants.54,55 This increase is exclusively seen after chronic use, thus corresponding to the onset clinical antidepressant effects with these therapies. Additional evidence that relates upregulation of these pathways and antidepressant treatment comes from antidepressant-like performance in behavioral models.

The findings of a number of studies do not recommend the use of PTT or PT as a guide for appropriate factor VIII replacement, since the values of these tests may be within normal range at hazardously low plasma levels of factor VIII.2 Therefore, it might be legitimate to suggest that hemophilia A sellckchem patients should be managed in a hospital with facilities to measure plasma levels of factor VIII. Venous thromboembolism occurs more Inhibitors,research,lifescience,medical in the elderly, patients with inherited thrombophilia diseases, and those undergoing high risk surgeries such as splenectomy, or pelvic or orthopedic surgery.12 Although the occurrence of spontaneous or post surgery

thromboembolism in patients with hemophilia A has been reported in literatures 6,13-15, the

risk of hemorrhage in Inhibitors,research,lifescience,medical such patients is usually greater than the risk of thrombosis.7 Hemophilia A cases undergoing major surgeries are rare, and have been rarely encountered by us. The case in the present study was a young male without any risk factor for hospital acquired venous thromboembolism. He had been treated occasionally with factor VIII concentrates at the time of bleedings. Although thrombophilia screening had never been performed, he didn’t have any significant risk factor for thromboembolism. The fact that the patient had hemophilia made us fear more Inhibitors,research,lifescience,medical from a catastrophic hemorrhagic event rather than thromboemboli, therefore we cautiously prepared adequate factor VIII concentrate for Inhibitors,research,lifescience,medical the patient, and double-ligated all of the vessels and injured tissues in the operation field. With this hemostatic treatment strategy, we never thought an unexpected thromboembolic event might occur. However, during treatment with factor VIII concentrate for

replacement therapy, the balance of risk turned in favor of thrombosis and pulmonary emboli. It has been proposed that individuals with hemophilia A, who receive factor VIII for replacement Inhibitors,research,lifescience,medical to achieve near normal levels, have a risk of thromboembolism approximating that of the general population.16 Moreover, it has been suggested that patients with hemophilia A have an equal chance of having an inherited thrombophilia as the general population. This is thought to explain the fact that some patients with severe hemophilia (factor VIII activity < 1%) have a milder clinical picture of the disease. The risk of thromboembolism in hemophilia A patients is particularly Dacomitinib important if they were to be placed in a situation with high risk for thromboembolic disease, while being fully replaced with factor VIII to achieve normal levels of the factor. Deep vein thrombosis and subsequent pulmonary embolism has been documented in hemophilia A patients undergoing high risk orthopedic surgeries.17 Also, it is well documented that children with hemophilia and long term portocaths are at risk of upper limb thrombosis.

The results indicated that, similar to glucocorticoids and norepinephrine magnifying memory,33 CRH in the customer reviews amygdala modulated learning and memory for aversive events.83 While glucocorticoids are essential in the development of fear,84 perhaps by the induction of central

CRH, glucocorticoids, and CRH both play a larger role in the organization of behavior.85-87 Nonetheless, glucocorticoids are secreted Inhibitors,research,lifescience,medical under a number of experimental conditions in which fear, anxiety, novelty, and uncertainty are experimental manipulations.9,78,88-90 In contexts where there is loss of control, or the perception of a loss of control (worry is associated with the loss of control), glucocorticoids are secreted. This holds across a number of species, including humans; perceived control reduces the levels of Inhibitors,research,lifescience,medical glucocorticoids.88 These findings

are congruent with those of Curt Richter91 who observed an enlarged adrenal gland in stressed, fearful wild rats when compared with unstressed laboratory analogs. Glucocorticoids in the basolateral complex of the amygdala appear to be necessary for aversive and fear conditioning. For example, injection of the glucocorticoid receptor antagonist RU-486 into the basolateral complex of the amygdala will reduce the consolidation of aversive conditioning92 Inhibitors,research,lifescience,medical in addition to other forms of conditioning, including contextual fear.93 Other experiments have shown that glucocorticoid injections into the amygdala can facilitate aversive conditioning.33 Experiments like these, which use

post-training injection procedures, demonstrate that glucocorticoids are necessary for consolidation of the memory of aversive conditioning and Inhibitors,research,lifescience,medical may facilitate the memory process.94,95 Glucocorticoid levels impact on learned fear.94-97 For example, in one study rats received conditioning trials in which the unconditioned stimulus (footshock) was presented concurrently with the conditioned stimulus (auditory tone). For several days after conditioning the rats were treated with Inhibitors,research,lifescience,medical corticosterone; conditioned fearinduced freezing was enhanced.96 Corticosterone, by the induction of central CRH expression, facilitates fear-related behavioral responses.76 Thus, in one study looking at contextual fear conditioning, groups of rats that were chronically treated with Anacetrapib corticosterone displayed more fear conditioning than the vehicle-treated rats. Glucocorticoid antagonists disrupt contextual fear conditioning.94,95 Thus, the data suggest that repeated high levels of corticosterone can facilitate the retention of contextual fear conditioning, perhaps by the induction of CRH gene expression in critical regions of the brain such as the amygdala. Importantly, amygdala infusion of corticosterone aimed at the central nucleus also increases milder forms of anxiety as measured with rats in the elevated plus maze.