Treatment Of Anxiety-related Disorders Research Articles

The Mechanism of Anxiolytic Effects of Moringa oleifera Leaf Extracts Associated with Significant Differential Expression of Crhb, Faah2a, Mao, and Pah Genes in Danio rerio

The search and development of new therapeutic agents from medicinal plants to alleviate anxiety is well justified due to the increasing cases of anxiety disorder and lack of effective treatment. Moringa oleifera has been used traditionally to treat anxiety. However, there is still lack of understanding on the mechanism for its anxiolytic effect. The purpose of this study was to investigate the anxiolytic effects and the mechanism of ethanolic extracts of the leaves of M. oleifera (MOLE) by observing behavioural changes of the Danio rerio and the differential gene expression analysis using custom RT2 Profiler PCR array. A 14-day chronic behaviour study was conducted using three concentrations of MOLE (500 mg/L, 1000 mg/L and 2000 mg/L) fluoxetine as the positive control. Stress-induced D. rerio treated with 1000 mg/L MOLE showed the lowest level of anxiety compared to other groups as evidenced by a decrease in freezing episodes and freezing time, increased entries into the light region. The fish also showed significant changes in the expression of crhb, faah2a, mao, and pah genes. MOLE with the presence of quercetin and kaempferol are believed to exert its anxiolytic effects through differential expression of gene (i) modulating the function of GABAA receptor (crhb), (ii) inhibiting the expression of nitric oxide synthase (NOS) and the production of nitric oxide, (iii) increasing the AEA levels in the brain (faah2a), (iv) increasing the level of dopamine levels in the brain (mao). These findings provide valuable insights into the potential use of MOLE as a treatment for anxiety-related disorders as well as the significance of the molecular pathways involved in its anxiolytic properties.

Inhibitory Learning during Exposure Treatment in Anorexia Nervosa: A Practical Guide.

Exposure therapy is known to be an effective intervention in the treatment of anxiety-related disorders. In eating disorders, such as anorexia nervosa, anxiety and avoidance are identified as maintenance factors. Therefore, they may constitute an important treatment target, suitable for the use of exposure therapy. Remarkably, exposure techniques to target fears and avoidance behaviors are not commonly used in the treatment of anorexia nervosa. We present a practical guide for the implementation of exposure therapy in the treatment of anorexia nervosa. We outline how exposure therapy is supposed to work according to the inhibitory learning model and how the exposure intervention can be designed for individuals with anorexia nervosa. Practical examples are provided through the case presentation of a patient with anorexia nervosa who completed 31 exposure sessions that focused on her fears of food, eating, weight, weight gain, their feared social consequences and the associated safety behaviors.

The effects of stress on avoidance in rodents: An unresolved matter.

In the face of a possible threat, a range of physiological (e.g., increased heart rate) and behavioral (e.g., avoidance or escape) responses are recruited. Here, we will focus on avoidance, in its persistent form one of the core symptoms of anxiety disorders and obsessive-compulsive disorder. The initial goal of fear and avoidance responses is to increase survival, but if they become persistent or overgeneralize, they can disrupt normal daily functioning, and ultimately even result in anxiety-related disorders. Relatedly, acute stress responses promote adaptation and survival, while chronic stress has been found to aggravate pathophysiology. Thus, stress might trigger the transition from adaptive to maladaptive responses, e.g., from goal-directed to persistent avoidance. Animal models are prime tools to unravel if and how stress influences avoidance. This is typically done by performing stress inductions prior to the assessment of (passive or active) avoidance behavior. Despite its clinical relevance, the current literature on this topic is fragmented, and an overall conclusion is lacking. In this Review, we first recapitulate the state of the art regarding stress and active as well as passive avoidance procedures. We then summarize the behavioral effects of acute and chronic stress on active and passive avoidance, and discuss the main neurobiological findings of the field. Finally, we highlight possible reasons for the largely contradictory findings in the literature and we propose strategies to further unravel the effect of stress on avoidance behavior. A deeper understanding of this currently unresolved matter may provide further insights in the etiology and treatment of anxiety-related disorders.

Cannabidiol Prevents Spontaneous Fear Recovery after Extinction and Ameliorates Stress-Induced Extinction Resistance.

Cannabidiol, the main non-psychotropic constituent of cannabis, has potential as a treatment for anxiety-related disorders since it reduces learned fear expression and enhances fear extinction. The return of fear over time after successful extinction and stress-induced extinction resistance are potential barriers to the treatment of these disorders with extinction-based psychological therapy. In two experiments using rats subjected to auditory fear conditioning, we determined the effects of systemic cannabidiol treatment on (1) delayed extinction and later spontaneous fear recovery, and (2) extinction resistance caused by immediate extinction (the immediate extinction deficit (IED)). In Experiment 1, cannabidiol was given before delayed extinction occurring 24 h after conditioning, with extinction recall and spontaneous fear recovery tested drug-free 1 and 21 days after extinction, respectively. We found that cannabidiol had no effect on extinction recall but it prevented spontaneous fear recovery. In Experiment 2, the IED procedure was first validated, with immediate extinction occurring 30 min after conditioning. We confirmed that immediate extinction impaired extinction recall, compared to delayed extinction. Next, cannabidiol was given before immediate or no extinction, with extinction recall tested drug-free the next day. We found that cannabidiol rescued the IED, which did not involve effects on fear memory consolidation. In summary, cannabidiol prevented spontaneous fear recovery after delayed extinction and ameliorated extinction resistance caused by immediate extinction. Although the pharmacological mechanisms underlying these effects remain to be determined, our results add to evidence indicating that cannabidiol might prove useful as an adjunct for potentiating the psychological treatment of anxiety-related disorders.

Neural dynamics and coupling underlying uncertain anticipatory conflicts in anxious individuals.

Anticipation plays an important role in cognitive control and related psychiatric disorders such as anxiety. However, anticipation processing of conflicts in anxious individuals and the underlying brain mechanisms remain unknown. Using a newly designed cue-flanker task, we observed faster responses to congruent flankers with certain cues in individuals with high trait anxiety (HTA) than those with low trait anxiety (LTA). Microstate analyses revealed less occurrence of cue-evoked microstates in HTA than LTA. Importantly, the less occurrence of specific state was correlated to the larger flanker effect in HTA, suggesting that deficient conflict control in anxiety is associated with abnormal vigilance-related dynamic processing during anticipation. Delta-beta coupling at anticipation stage mediated the association between the level of anxiety and reaction time in conflict processing with uncertain cues in HTA, suggesting the mediatory role of delta-beta coupling in anticipatory conflict processing of anxious individuals. These results suggest hyperactive anticipatory processing of goal-relevant information for the upcoming conflict in anxious individuals. Our findings provide neurocognitive evidence for altered anticipatory cognitive control in anxious individuals and have important implications for diagnosis and treatment of anxiety-related disorders.

Fear and Anxiety in COVID-19: Preexisting Anxiety Disorders

The general population has experienced a significant elevation in fear and anxiety during COVID-19 both as a direct result of the virus but also due to measures taken to prevent it spreading, such as the need to stay inside and increase hand-washing. Lockdown has been used in many/most countries to prevent widespread infection. The advice and imposed actions are necessary to prevent the virus from spreading, but they might exacerbate the problems experienced by people with a preexisting anxiety-related disorder. The treatment of anxiety-related disorders can be provided while in quarantine. Staying at home in self-isolation does not preclude obtaining psychological treatment for anxiety-related disorders. Dealing with cognitive biases, over-estimations of threat, intolerance of uncertainty, inflated responsibility and excessive safety behavior, are useful clinical directions.

Clonazepam-induced lichenoid drug eruption: a case report

BackgroundLichenoid drug eruption is rare and can mimic idiopathic lichen planus and other dermatoses. Clonazepam, a commonly used drug for the treatment of anxiety-related disorders and seizures, is known to be an unlikely cause of cutaneous adverse effects. Only one case report of LDE due to clonazepam has been reported.Case presentationA 81-year-old male patient with Alzheimer’s disease developed a lichenoid eruption after taking clonazepam. He developed a violaceous scaly patch on his lower extremities, from both buttocks to the feet. The cutaneous eruption resolved 2 months after cessation of clonazepam and with initiation of corticosteroid therapy.ConclusionA skin eruption that develops after clonazepam administration can be a lichenoid drug eruption, which is less likely to resolve spontaneously and requires discontinuation of clonazepam administration.

Pharmacological and pharmacokinetic effect of a polyherbal combination with Withania somnifera (L.) Dunal for the management of anxiety

Ethnopharmacological relevanceIn the Indian system of medicine, Withania somnifera (L.) Dunal, Hemidesmus indicus (R.Br.), Aegle marmelos (L.) Correa, Emblica officinalis Gaertn, Ocimum sanctum (L.) has been mentioned as a remedy for the treatment of anxiety related disorders. Based on their folklore use, a polyherbal combination was derived for the management of anxiety. Aim of the studyThe present study is aimed to find the best polyherbal combination (PHC), in terms of its pharmacological action, out of two PHC, namely PHC1 and PHC3, prepared based on the previous studies conducted and to carry out the pharmacokinetic (PK) study of the best combination (PHC3). Materials and methodsPharmacological activities include elevated plus maze model and hole-board test for anti-anxiety screening, gamma amino-butyric acid (GABAA) measurement in brain tissues and superoxide dismutase, lipid peroxidation and reduced glutathione measurement for anti-oxidant screening. ResultsPHC3 (100 mg/kg) produced statistically significant (p < 0.05) effect on all the pharmacological outcome measures when compared to alprazolam standard. Therefore, it was chosen for PK study. PK study was carried out using Liquid Chromatography Mass Spectroscopy technique with respect to Withaferin-A. PK parameters such as maximum plasma concentration (Cmax), 16.78 ± 5.32 ng/mL; time of maximum concentration (Tmax), 18 ± 0.12min; half-life (T1/2) 61.20 ± 9.87min; mean residual time (MRT), 7.53 h s; area under the concentration versus time curve (AUC0-1), 1678 ± 34.13 ng/mL; area under the concentration versus time curve from zero to infinity (AUC0-∞), 1705 ± 28.87 ng/mL; total clearance (CL), 290.67 ± 15.89 mL/min and volume of distribution (Vd) 0.054 L were calculated. ConclusionsThe results of the studies revealed that PHC3 possessed significant anxiolytic, anti-oxidant activities and enhanced expression of GABAA mediated inhibition when compared to PHC1. Withaferin-A in PHC3 exhibited a rapid oral absorption in rat plasma. The findings of this study greatly help to provide useful evidence for the development of suitable formulation using PHC3.

Inhibition of RPTPβ/ζ blocks ethanol-induced conditioned place preference in pleiotrophin knockout mice

Pleiotrophin (PTN) and Midkine (MK) are neurotrophic factors that are upregulated in the prefrontal cortex after alcohol administration and have been shown to reduce ethanol drinking and reward. PTN and MK are endogenous inhibitors of Receptor Protein Tyrosine Phosphatase (RPTP) β/ζ. Interestingly, pharmacological inhibition of RPTPβ/ζ reduces ethanol consumption and blocks ethanol-induced conditioned place preference (CPP) in wild type mice. Since PTN-knockout (Ptn−/−) mice are more sensitive to the conditioning effects of alcohol, we aimed to test the effects of MY10, a small-molecule inhibitor of RPTPβ/ζ, on ethanol-induced CPP in Ptn−/− mice. The data presented here demonstrate for the first time that a regular dose of MY10, known to block ethanol consumption and reward in wild type mice, also blocks the rewarding effects of ethanol in the more vulnerable individuals lacking PTN, the endogenous inhibitor of RPTPβ/ζ. In addition, since MY10 readily penetrates the blood brain barrier (BBB), we tested its effects in a series of behavioural tests in Ptn+/+ and Ptn−/− mice. The data indicate that MY10 does not cause gross behavioural effects in wild type mice. However, MY10 tended to induce anxiolytic effects in Ptn−/− mice in the elevated plus maze paradigm. Overall, the data indicate that MY10 rescues Ptn−/− mice from their increased susceptibility to the conditioning effects of ethanol and may induce anxiolytic effects in individuals with reduced or absent PTN functions. Further studies are needed to confirm the potential of pharmacological inhibition of RPTPβ/ζ as a new therapeutic strategy in the treatment of anxiety-related disorders.

Modulating Effects of Cholecalciferol Treatment on Estrogen Deficiency-Induced Anxiety-Like Behavior of Adult Female Rats.

Vitamin D can be one of the candidate substances that are used as additional supplementation in the treatment of anxiety-related disorders in women with estrogen imbalance. The aim of the present study was to examine the effects of chronic cholecalciferol administration (1.0, 2.5 or 5.0 mg/kg/day, s.c.) on the anxiety-like behavior and monoamines levels in the rat hippocampus following ovariectomy in female rats. Cholecalciferol was given to ovariectomized (OVX) rats and OVX rats treated with 17β-estradiol (17β-E2, 0.5 μg/rat, s.c.). The anxiety-like behavior was assessed in the elevated plus maze (EPM) and the light-dark tests (LDT), locomotor and grooming activities were assessed in the open-field test (OFT). Cholecalciferol in high doses alone or in combination with 17β-E2-induced anxiolytic-like effects in OVX and OVX rats treated with 17β-E2 as evidenced in the EPM and LDT tests, and increased grooming activity in the OFT test. We found that DA and 5-HT levels increased while 5-HT turnover in the hippocampus decreased in these groups of OVX rats. Our results indicate that cholecalciferol in high doses has a marked anxiolytic-like effect due to an increase in the monoamines levels in the experimental rat model of estrogen deficiency.

Cannabidiol as a Potential Treatment for Anxiety Disorders.

Cannabidiol (CBD), a Cannabis sativa constituent, is a pharmacologically broad-spectrum drug that in recent years has drawn increasing interest as a treatment for a range of neuropsychiatric disorders. The purpose of the current review is to determine CBD's potential as a treatment for anxiety-related disorders, by assessing evidence from preclinical, human experimental, clinical, and epidemiological studies. We found that existing preclinical evidence strongly supports CBD as a treatment for generalized anxiety disorder, panic disorder, social anxiety disorder, obsessive-compulsive disorder, and post-traumatic stress disorder when administered acutely; however, few studies have investigated chronic CBD dosing. Likewise, evidence from human studies supports an anxiolytic role of CBD, but is currently limited to acute dosing, also with few studies in clinical populations. Overall, current evidence indicates CBD has considerable potential as a treatment for multiple anxiety disorders, with need for further study of chronic and therapeutic effects in relevant clinical populations.

ANTIANXIETY EFFECT OF ETHANOLIC EXTRACT OF LEAVES OF TYLOPHORA INDICA IN WISTAR ALBINO RATS

Pathological anxiety is one of the most commo n mental disorders in humans. Anxiolytic drugs, mostly belonging to the benzodiazepine (BDZ) group and serotoner gic groups are widely used to treat anxiety. However the clinical uses of these established drugs are associated with lot of adverse effects. Therefore the development of new agent poss essing anxiolytic effect with minimal or no adverse effects would be of great importance in the treatment of anxiety related disorders. Very high importance is given to the phytoconstituents by the scientific community fo r a new anxiolytic agent which is devoid of side effects/ minimal adverse effects. In this research work t he ethanolic extract of Tylophora indica (300 mg/kg body weight ) was administered oral for ten days to Wistar albino rats for screening its anxiolytic effect by using Elevated Plus Maze (EPM) and Light Dark Arena (LDA) test. The results of our study demons trated that the ethanolic extract of Tylophora indica has significant anxiolytic activity in EPM and LDA models of anxiety. Keyw ords : Anxiety, Wistar albino rats, Tylophora indica, E thanolic extract, Anxiolytic activity

The active alkaloids of Gelsemium elegans Benth. are potent anxiolytics

An increasing number of herbal products has been introduced to treat anxiety and depression. Gelsemium elegans Benth (G. elegans) is a well-known herbal plant in Asia. Four major alkaloids (gelsemine, koumine, gelsevirine, and gelsenicine) have been isolated from G. elegans. Recently, interest has arisen to investigate the pharmaceutical potential of G. elegans alkaloids in the context of neuropsychopharmacology. We investigated whether G. elegans alkaloids are capable of producing anxiolytic and antidepressant effects in mouse models. In particular, we examined whether the anxiolytic action of G. elegans alkaloids is due to the agonist effects of glycine receptor in the brain. Two mouse models (elevated plus-maze and light-dark transition model) were used to examine potential anxiolytic effects. Forced swim test and tail suspension test were used to test the antidepressive action of G. elegans alkaloids. Moreover, we also explored the anxiolytic mechanisms of G. elegans alkaloids by intracerebroventricular administration of strychnine, an antagonist of glycine receptor, in the elevated plus-maze. Gelsemine, koumine, and gelsevirine, but not gelsenicine, exhibited potent anxiolytic effects in the two anxiety models. None of the four G. elegans alkaloids exerted antidepressant effects in the two depression models. None of G. elegans alkaloids impaired spontaneous motor activities. The intracerebroventricular administration of strychnine significantly antagonized the anxiolytic effects of gelsemine, koumine, and gelsevirine administrated subcutaneously. Gelsemine, koumine, and gelsevirine could be developed as the treatment of anxiety-related disorders in human patients. Their anxiolytic mechanism may be involved in the agonist action of glycine receptor in the brain.

Anxiolytic effect of homeopathic preparation of Pulsatilla nigricans in Swiss albino mice

The homeopathic preparation of Pulsatilla nigricans is used in the treatment of anxiety related disorders. Though in clinical use for many years, the anxiolytic activity of Pulsatilla nigricans (Puls) has not been evaluated experimentally. Hence the present study was conducted in Swiss albino mice to evaluate the anxiolytic activity of Puls and compare its activity with the standard anxiolytic drug, diazepam. Twenty four mice were divided into 4 groups of 6 animals each, control, standard and two test groups. The control group was treated Ethyl alcohol 10 ml/kg. The standard group received Diazepam, 1 mg/kg. Puls 3x and 6x solutions were given at the dose of 10 ml/kg to the test groups. All animals were given the test and control treatments orally for 15 days. The anxiolytic effect was tested on days 1, 8 and 15 using the Elevated Plus Maze (EPM) and Open Field Test (OFT). Both diazepam and Puls showed significant anxiolytic activity in EPM and OFT test compared to control. The total number of entries and time spent in open arm in EPM was increased by both diazepam and Puls, the effect of 3x dilution of Puls was greater than diazepam. In the OFT the number of squares crossed, rearing and assisted rearings decreased with both diazepam and Puls compared to control and the anxiolytic effect of diazepam was greater than Puls. The anxiolytic effect is greater for the 3x dilution than 6x dilution of Puls. The study showed an anxiolytic effect of homeopathic preparation of Pulsatilla nigricans comparable to that found with a standard drug.

Chronic blockade of cannabinoid CB2 receptors induces anxiolytic‐like actions associated with alterations in GABAA receptors

The aim of this study was to explore the effects of CB(2) receptor agonist and antagonist in the regulation of anxiety-like behaviours. Effects of acute and chronic treatment with the CB(2) receptor agonist JWH133 and CB(2) receptor antagonist AM630 were evaluated in the light-dark box (LDB) and elevated plus maze (EPM) tests in Swiss ICR mice. CB(2) receptor, GABA(A) α(2) and GABA(A) γ(2) gene and protein expression in the cortex and amygdala of mice chronically treated with JWH133 or AM630 were examined by RT-PCR and Western blot. Effects of chronic AM630 treatment were evaluated in spontaneously anxious DBA/2 mice in LDB. Acute JWH133 treatment failed to produce any effect. Acute AM630 treatment increased anxiety and was blocked by pre-treatment with JWH133. Chronic JWH133 treatment increased anxiety-like behaviour whereas chronic AM630 treatment was anxiolytic in LDB and EPM tests. Chronic AM630 treatment increased gene and reduced protein expression of CB(2) receptors, GABA(A) α(2) and GABA(A) γ(2) in cortex and amygdala. Chronic JWH133 treatment resulted in opposite gene and protein alterations. In addition, chronic AM630 administration decreased the anxiety of DBA/2 mice in the LDB test. The opposing behavioural and molecular changes observed after chronic treatment with AM630 or JWH133 support the key role of CB(2) receptors in the regulation of anxiety. Indeed, the efficacy of AM630 in reducing the anxiety of the spontaneously anxious DBA/2 strain of mice strengthens the potential of the CB(2) receptor as a new target in the treatment of anxiety-related disorders.

Virtual reality and mobile phones in the treatment of generalized anxiety disorders: a phase-2 clinical trial

Several studies have demonstrated that exposure therapy--in which the patient is exposed to specific feared situations or objects that trigger anxiety--is an effective way to treat anxiety disorders. However, to overcome a number of limitations inherent in this approach--lack of full control of the situation, costs and time required, etc.--some therapists have started to add virtual reality (VR) to the in vivo exposure-based therapy, providing in-office, controlled exposure therapy. Compared to the in vivo exposure, VR Exposure Therapy (VRET) is completely controlled: the quality, the intensity and the frequency of the exposure are decided by the therapist, and the therapy can be stopped at any time if the patient does not tolerate it. Moreover, the flexibility of a virtual experience allows the patient to experience situations that are often much worse and more exaggerated than those that are likely to be encountered in real life. However, a critical issue underlying the use of VRET in the treatment of anxiety-related disorders is the lack of a virtual reality system in the patient's real-life context. In this paper, we present a clinical protocol for the treatment of Generalized Anxiety Disorders (GAD) based on the ubiquitous use of a biofeedback-enhanced VR system. The protocol includes the use of a mobile exposure system allowing patients to perform the virtual experience in an outpatient setting. A between-subjects study, involving 25 GAD patients, was carried out to verify the efficacy of the proposed approach. The clinical data in this pilot study seemed to support the efficacy of the ubiquitous approach.

What makes people anxious about pain? How personality and perception combine to determine pain anxiety responses in clinical and non-clinical populations

Although anxiety has both dispositional and situational determinants, little is known about how individuals' anxiety-related sensitivities and their expectations about stressful events actually combine to determine anxiety. This research used Information Integration Theory and Functional Measurement to assess how participants' physical concerns sensitivity (PCS) and event expectancy are cognitively integrated to determine their anxiety about physical pain. Two studies were conducted – one with university students and other with anxiety clinic patients – in which participants were presented with multiple scenarios of a physically painful event, each representing a different degree of event probability from which subjective expectancies were derived. Independent variables included PCS (low, moderate, and high) and event expectancy (low-, medium-, high-, and non-probability information). Participants were asked to indicate their projected anxiety (dependent measure) in each expectancy condition in this 3×4 mixed, quasi-experimental design. The results of both studies strongly suggest that PCS and event expectancy are integrated additively to produce these pain anxiety scores. Additional results and their implications for the treatment of anxiety-related disorders are also discussed.

Progress in the Developement of Positive Allosteric Modulators of the Metabotropic Glutamate Receptor 2

The metabotropic glutamate type 2 (mGlu2) receptor is a G-protein coupled receptor (GPCR) expressed on presynaptic nerve terminals where it negatively modulates glutamate and GABA release. Mixed mGlu2/mGlu3 orthosteric agonists such as LY354740 have shown activity in a range of preclinical animal models of anxiety and schizophrenia. Clinical work with LY354740 demonstrated activity in a CO(2) inhalation study suggesting application in the treatment of anxiety related disorders. Subsequently, a related prodrug LY2140023 demonstrated improvements in positive and negative symptoms in patients suffering from schizophrenia. These molecules exhibit combined mGlu2/mGlu3 activity although there is evidence from knock-out studies that preclinical anti-psychotic effects may be mediated via the mGlu2 receptor. An alternative avenue for modulating GPCRs is to act via allosteric mechanisms, binding at a different site from the orthosteric agonist. Since the first discovery of mGlu2 positive allosteric modulators (PAMs) such as 2,2,2-TEMPS and BINA, multiple families of mGlu2 modulators have been reported and several have entered into clinical development. This review focuses on recent advances in the development of novel mGlu2 PAMs by analysis of compounds disclosed in research articles and patent literature between 2007 and 2010.

Anxiolytic-like property of risperidone and olanzapine as examined in multiple measures of fear in rats

Atypical antipsychotics are also used in the treatment of anxiety-related disorders. Clinical and preclinical evidence regarding their intrinsic anxiolytic efficacy has been mixed. In this study, we examined the potential anxiolytic-like effects of risperidone and olanzapine, and compared them with haloperidol, chlordiazepoxide (a prototype of sedative–anxiolytic drug) or citalopram (a selective serotonin reuptake inhibitor). We used a composite of two-way avoidance conditioning and acoustic startle reflex model and examined the effects of drug treatments during the acquisition phase (Experiment 1) or extinction phase (Experiments 2 and 3) on multiple measures of conditioned and unconditioned fear/anxiety-like responses. In Experiment 4, we further compared risperidone, olanzapine, haloperidol, citalopram and chlordiazepoxide in a standard elevated plus maze test. Results revealed three distinct anxiolytic-like profiles associated with risperidone, olanzapine and chlordiazepoxide. Risperidone, especially at 1.0 mg/kg, significantly decreased the number of avoidance responses, 22 kHz ultrasonic vocalization, avoidance conditioning-induced hyperthermia and startle reactivity, but did not affect defecations or time spent on the open arms. Olanzapine (2.0 mg/kg, sc) significantly decreased the number of avoidance responses, 22 kHz vocalization and amount of defecations, but it did not inhibit startle reactivity and time spent on the open arms. Chlordiazepoxide (10 mg/kg, ip) significantly decreased the number of 22 kHz vocalization, avoidance conditioning-induced hyperthermia and amount of defecations, and increased time spent on the open arms, but did not decrease avoidance responses or startle reactivity. Haloperidol and citalopram did not display any anxiolytic-like property in these tests. The results highlight the importance of using multiple measures of fear-related responses to delineate behavioral profiles of psychotherapeutic drugs.

Information integration and emotion: How do anxiety sensitivity and expectancy combine to determine social anxiety?

Relatively little is known about the integration of people's fear-related dispositions and their expectations about stressful events. This research used information integration theory to examine how participants’ anxiety sensitivity and event expectancy are integrated to determine their social anxiety. Three studies were conducted—two with university students and one with anxiety clinic patients—in which participants were presented with multiple scenarios of a socially embarrassing event, each representing a different degree of event probability, from which subjective expectancies were derived. Independent variables included anxiety sensitivity (low, moderate, high) and event expectancy (low, medium, high, no probability information). Participants were asked to indicate their anxiety (dependent measure) in each expectancy condition in this 3 × 4 mixed, quasi-experimental design. The results of all three studies strongly suggest that anxiety sensitivity and event expectancy are integrated additively to produce social anxiety. Additional results and their implications for the treatment of anxiety-related disorders are also discussed.