Fear and anxiety disorders are potentially crippling conditions that often stem from past experience of trauma and chronic stress. One clear feature of these disorders is the failure to use proximate spatial and contextual information presented in the environment to regulate reflexive physiological threat responses. The central nervous system networks that govern spatial navigation and contextual learning and memory are a series of complex circuitries in which the hippocampus is integrally involved. Deficits in hippocampal function have been linked to severe anterograde and mild retrograde amnesia of semantic and episodic memory, and specific deficits in contextual processing. These deficits manifest as failure to distinguish between the details of contexts that help predict for danger or safety and can thus lead to the overexpression of threat responses that compose the behavioral symptoms of fear disorders. The dentate gyrus (DG) is a subdivision of the hippocampus that serves as the first filter of excitatory flow through the hippocampus. The DG is hypothesized to function in “pattern separation” or the dissociation of similar inputs into dissimilar outputs. Failure in this domain leads to generalization between contexts, a common feature of pathology. Pituitary adenylate cyclase activating polypeptide (PACAP) and the PAC1 receptor are associated with multiple behavioral disorders such as post-traumatic stress disorder, schizophrenia, and bipolar disorder. Mutations in the PAC1 receptor gene are associated with hypervigilance, and modified amygdalar and hippocampal activity. These results are mirrored by rodent studies where central PACAP infusion causes anxiety-like behavior, pain hypersensitivity, anorexia, and reinstatement of drug-seeking. PAC1 receptor transcript is found in high abundance in granule cells of the dentate gyrus and potentiation of DG synapses is impaired in PAC1 knockout mice. PACAP is known to have effects of long-duration, such as those in injury repair, growth, and development, but it also can affect ion channel physiology to control neuronal excitability through several parallel intracellular signaling cascades including those dependent on adenylyl cyclase, phospholipase C, and extracellular signal regulated kinase. Accumulated evidence suggests that recruitment of extracellular signal regulated kinase can be through either adenylyl cyclase-, phospholipase C-, or a receptor endocytosis-dependent mechanism. The experiments described in this dissertation address the role of PACAP in the DG in regulating expression of fear behavior, the effects of PACAP on the excitability of DG granule cells, and the signaling pathways and ion channels responsible for these effects. We found that PACAP infused into the DG amplifies expression of fear to a context but does not affect fear acquisition. Electrophysiology studies demonstrate that treating DG neurons with PACAP increases their excitability, and that parallel signaling mechanisms recruit extracellular signal regulated kinase to drive this excitability. Furthermore, these effects on excitability are attenuated by blocking a persistent inward sodium current. This work represents novel regulation of the DG and its impacts on behavior and identifies a current that likely participates in modulating granule cell excitability in multiple domains. In aggregate, this research traces the path from ligand, to receptor and intracellular signaling, to neurophysiology in order to propose a comprehensive description of behavioral regulation by these processes.

In the 1960s, the government formed the President's Commission on Law Enforcement and Administration of Justice to looked at the problem of crime and fear of crime in modern American society. In addition to looking at these issues, the Commission also looked at ways to potentially reduce both crime and fear of crime. One of the primary outcomes of the Commission's report was that policing agencies in the United States needed to fundamentally alter the way they served their communities, notably by transitioning to community-oriented policing (COP). Starting in the 1970s, law enforcement agencies around the nation began to embrace the COP philosophy in the hopes that it would effectively reduce crime. A plethora of research suggests that the crime reduction benefits of COP are dubious at best; however, COP shows great promise in reducing fear of crime in neighborhoods. However, scholars remain uncertain as to why COP can effectively reduce fear. The uncertainty surrounding the efficacy of COP lies in the incomplete theoretical understanding of fear of crime. Three largely divergent fear of crime models have been developed. The first, the social integration model, posits that fear is influenced by the degree to which a person is integrated into their community. The thought being that the more socially integrated a person is, the stronger the sense of informal social and thus the lower the fear of crime. Research generally--although not always--supports this notion. Other scholars developed the disorder model, which posits that disorderly conditions or other signs of incivility can lead residents to feel as though informal social control has broken down, and thus elevate levels of fear. Again, this notion is well supported in the research. The final model suggests fear of crime is a result of sociodemographic differences (e.g., gender and age) that make a person feel more vulnerable to victimization, and thus those feeling most vulnerable exhibit the highest levels of fear. The findings from this so-called vulnerabilities model receive inconsistent support in the research. The problem with the extant fear of crime research is that it largely relies on singular explanations of fear. In other words, it operates from the premise that one of the models described above is responsible for residents' levels of fear. Recently, scholars have begun developing multimodel explanations in an effort to improve criminologists' ability to explain fear of crime. However, this multimodel approach is not a complete theoretical model of fear because it fails to account for the likely existence of a reciprocal effect between fear of crime and social integration. Further, it fails to account for the effects of social context may exert on fear and the way in which neighborhood differences may condition the individual-level fear of crime relationships. This dissertation, using two data sources, attempts to predict fear of crime using a more complete fear of crime model than those used in much of the prior research. The first source of data used is the 2004 Hillsborough County Sheriff's Office community survey (N=1898), which was distributed to a random sample of households in unincorporated Hillsborough County. Additionally, to create measures of social context, this dissertation utilizes data from the 2000 United States Census for census designated places in unincorporated Hillsborough County--which serve as the proxy for neighborhoods (N=30). Based on theory and prior research, it was hypothesized that the best fear of crime model would contain elements from all three theoretical models developed in prior research. Additionally, it was hypothesized that there would be a significant and negative reciprocal effect from fear of crime to social integration. Finally, it was hypothesized that social context would condition the relationships between individual-level fear of crime predictors. As predicted by the hypothesis, the empirically strongest fear of crime model did contain elements from all three explanatory fear of crime models. Additionally as hypothesized, there was a significant reciprocal relationship between fear of crime and social integration. However, contrary to expectations the relationship was positive. In other words, fear of crime motivated residents to become more socially integrated in their neighborhoods. Finally, as hypothesized social context did condition the effects of the individual-level variables. However, contrary to the hypotheses proffered, social context augmented the size of the effect between the individual-level variables. The findings from this dissertation offer some interesting insights for scholars and posivy makers alike. The findings suggest that it is imperative to use a more complete (e.g., multimodel) approach when explaining fear of crime. Additionally, it is necessary to account for the reciprocal relationship between fear of crime and social integration; otherwise research will yield deceptive parameter estimates for social integration on fear of crime. Lastly, social context matters and needs to be considered in further research. However, the theoretical model in this dissertation--while a step forward--does not represent the theoretical model to explain fear of crime. The results suggest that the model may be even more complex than the model presented here. The results of this dissertation for policy makers suggest that community oriented policing strategies are likely an effective mechanism for reducing residents fear of crime for two reasons; 1) the strengthening of social integration programs in neighborhoods and 2) focusing on reducing disorder problems in neighborhoods. Study strengths and limitations, as well as directions for future research are discussed.

Aberrations in brain serotonin (5-HT) neurotransmission have been implicated in psychiatric disorders including anxiety, depression and deficits in learning and memory. Many of these disorders are treated with drugs which promote the availability of 5-HT in the synapse. Selective serotonin uptake inhibitors (SSRIs) are known to stimulate the production of new neurons in the hippocampus (HPC) by increasing synaptic concentration of serotonin (5-HT). However, it is not clear which of the 5-HT receptors are involved in behavioral improvements and enhanced neurogenesis. The current study aimed to investigate the effects of 5HT2A agonists psilocybin and 251-NBMeO and the 5HT2A/C antagonist ketanserin on neurogenesis and hippocampal-dependent learning. Agonists and an antagonist to the 5-HT2A receptor produced alterations in hippocampal neurogenesis and trace fear conditioning. Future studies should examine the temporal effects of acute and chronic psilocybin administration on hippocampal-dependent learning and neurogenesis.

The experiments reported in this thesis studied the contributions of opioid and NMDA receptors to predictive fear learning, as measured by freezing in the rat. The first series of experiments (Chapter 2) used a within-subject one-trial blocking design to study whether opioid receptors mediate a direct action of predictive error on Pavlovian association formation. Systemic administrations of the opioid receptor antagonist naloxone or intra-vlPAG administrations of the selective μ-opioid receptor antagonist CTAP prior to Stage II training prevented one-trial blocking. These results show for the first time that opioid receptors mediate the direct actions of predictive error on Pavlovian association formation. The second series of experiments (Chapter 3) then studied temporal-difference prediction errors during Pavlovian fear conditioning. In Stage I rats received CSA ?? shock pairings. In Stage II they received CSA/CSB ?? shock pairings that blocked learning to CSB. In Stage III, a serial overlapping compound, CSB → CSA, was followed by shock. The change in intra-trial durations supported fear learning to CSB but reduced fear of CSA, revealing the selective operation of temporal-difference prediction errors. This bi-directional change in responding was prevented by systemic NMDA receptor antagonism prior to Stage III training. In contrast opioid receptor antagonism differentially affected the learning taking place during Stage III, enhancing learning to CSB while impairing the loss of fear to CSA. The final series of experiments (Chapter 4) then examined potential neuroanatomical loci for the systemic effects reported in Chapter 3. It was observed that intra-BLA infusion of ifenprodil, an antagonist of NMDA receptors containing the NR2B subunit, prevented all learning during Stage III, whereas intra-vlPAG infusion of the μ-opioid receptor antagonist CTAP facilitated learning to CSB but impaired learning to CSA. These results are consistent with the suggestion that opioid receptors in the vlPAG provide an important contribution to learning. Importantly, this contribution of the vlPAG is over and above its role in producing the freezing conditioned response. Furthermore, the findings of this thesis identify complementary but dissociable roles for amygdala NMDA receptors and vlPAG μ-opioid receptors in predictive fear learning.

The basolateral complex of the amygdala (BLA) is a key component of the neuronal circuitry underlying the acquisition and the extinction of Pavlovian conditioned fear. The present series of experiments examined the role of neuronal activity and NMDA receptors (NMDAr) activation in the BLA on learning and relearning context conditioned fear and its extinction. Disruption of neuronal activity in the BLA prevented the acquisition of fear responses to a novel, a moderately familiar or a highly familiar context. It also prevented the reacquisition of fear responses to a conditioned or an extinguished context. Local blockade of NMDAr containing the NR2B subunit prior to training extinction or re-extinction impaired the short- and long-term loss of fear responses. In contrast, a similar blockade subsequent to training extinction or re-extinction left the long-term loss of fear responses unaffected. Disruption of neuronal activity in the BLA prior to training extinction and re-extinction depressed fear responses. It impaired the long-term loss of fear produced by extinction training but spared and even facilitated the long-loss of fear produced by re-extinction training when extinction had already been learned. The exact same outcome was observed when neuronal activity in the BLA was disrupted subsequent to training extinction and re-extinction. These findings suggest that the BLA is critical for both learning and relearning context conditioned fear. In contrast, the BLA is necessary for learning but not relearning extinction of conditioned fear. This implies that once extinction has been learned, others structures support the retrieval and the expression of extinction memory. This is consistent with current neural model of extinction that involves interactions between several neural substrates including the BLA and the medial prefrontal cortex.

The experiments reported in this thesis studied the mechanisms of expression of overexpectation of conditioned fear, as measured by freezing. In Stage I, rats were conditioned to fear a tone and a flashing light conditioned stimulus (CS) through pairings with a 0.5 mA, 1 s shock. In Stage II, overexpectation was trained by the reinforcement of a compound of these CSs with a shock of the same magnitude. Two compound ?? shock pairings produced an overexpectation effect, as measured by freezing to presentations of the tone alone, while further Stage II training caused over-training of overexpectation. Expression of the overexpectation effect produced by two compound ?? shock pairings could be prevented by pre-test injection of the benzodiazepine partial inverse agonist FG7142. This effect was dose-dependent and not due to state-dependent memory. Control experiments suggested that it was also not due to any general effect of FG7142 on the Pavlovian freezing response. Freezing to a tone that had been conditioned, but not subjected to any decremental training procedures, was unaffected by administration of FG7142 before either the conditioning or test session. FG7142 also did not affect freezing to a tone that had been subjected to an associative blocking procedure. The hypothesis that overexpectation of conditioned fear may be context-dependent was also tested. However, renewal was not observed. Rats that received Stage II training in a context distinct from the Stage I training context showed equivalent expression of overexpectation regardless of whether testing was conducted in the Stage I or Stage II training context. These results are consistent with the hypothesis that overexpectation, like extinction, leads to the imposition of a GABAA receptor-mediated mask on the fear CR. Moreover, they suggest that this masking of fear is the specific consequence of negative predictive error.

Eight experiments examined the role of the intertrial interval in the extinction of conditioned fear to a context. Rats were shocked in one context (A) but not in another (B) and freezing responses to Context A were extinguished. The interval between extinction trials was spent in the home cages. Experiments 1a and 1b showed that massed extinction trials produced better response loss but worse learning than spaced trials. Experiment 2 demonstrated that the interval between the final extinction trial and test mediated the level of responding on a test exposure. Experiments 3 and 4 showed that the duration of the extinction trial affected long term response loss, whereby long durations facilitate response loss compared to shorter durations. Subsequent experiments (Experiments 5 to 8) demonstrated that the first in the series of massed extinction trials reduced the associability of subsequent trials. Associability was restored by alternating extinction trials between Context A and Context B. The results are discussed in terms of the role accorded to self-generated priming in the models developed by A. R. Wagner (1978; 1981).

Cognitive-behavioural based models of chronic pain contend that appraisals of harm affect the individual�s response to pain. It has been suggested that fear of pain and/or anxiety sensitivity predispose individuals to chronicity. However, other factors such as pain self-efficacy are believed to mediate between experience of pain and disability. According to this view, pain is maintained through hypervigilance towards painful sensations and subsequent avoidance. Four studies were conducted in order to evaluate the structure of fear-avoidance models of chronic pain, and also, to examine the role of hypervigilance as an underlying mechanism in maintenance of pain. In study one, using a sample of 207 consecutive patients, two models were tested. First, fear of movement model as proposed by Vlaeyen et al. (1995a) was examined. It was found that negative affectivity has direct effects on the fear and avoidance of pain, which in turn, contributes to disability. In total, fear/avoidance accounted for a significant amount of the variance of disability. In addition, severity of pain was found to increase pain disability, while itself is influenced still by negative affectivity. These findings supported the model of fear of pain as described by Vlaeyen et al. (1995a). Further, we found that self-efficacy may mediate the impact of fear of pain on disability and reduces the perceived physical disability. At the same time, self-efficacy was shown to have direct reductive impact on disability. However, both studies indicated that people who are fearful in response to pain are more likely to develop disability, although self-efficacy may play a moderating role. In the studies one, two, and three, the role of hypervigilance in over attending to pain was investigated. In study one a large sample of 168 chronic pain patients were studied. Questionnaires measuring different aspects of pain and a computerised version of the Dot-Probe Task were administered. Four types of words related to different dimensions of pain and matched neutral words were used as stimuli. Reaction times in response to the stimuli were recorded. A factorial design 3x4x2x2 and ANOVAs were employed to analyse the data. Chronic pain patients showed a cognitive bias to sensory pain words relative to affective, disability, and threat-related words. However, contrary to expectations, those high in fear of pain responded more slowly to stimuli than those less fearful of pain. These results suggest that patients with chronic pain problems selectively attend to sensory aspects of pain. However, selective attention appears to depend upon the nature of pain stimuli. For those who are highly fearful of pain they may not only selectively attend to pain-related information but also have difficulty disengaging from those stimuli. In study two, 35 chronic pain patients were compared with the same number matched healthy subjects. Both groups completed measures of fear of pain, anxiety sensitivity, depression and anxiety, in addition to dot probe task. Results indicated that both groups show similar attentional bias to sensory words in comparison with other word types. However, the level of this biasness was higher for chronic pain patients. Lack of significant differences between patients and controls is discussed in the context of possible evolutionary value of sensitivity to pain as an adaptive reaction in healthy controls, and contrary, as a maladaptive response to pain in chronic pain patients. The results of the previous research suggest that chronic pain patients demonstrate cognitive biases towards pain-related information and that such biases predict patient functioning. The forth study examined the degree to which a successful cognitive-behavioural program was able to modify the observed attentional bias towards sensory pain words. Forty-two patients with chronic pain conditions for more than three months were recruited prior to commencing a cognitive-behavioural pain management program. Participants were assessed before the program, after the program and at one-month follow-up. Results confirmed that chronic pain patients exhibited biased attention towards sensory pain-related words at pre-treatment. These biases were still evident at post-treatment, but were no longer statistically significant at follow up. Multiple regression analyses indicated that the changes in attentional bias towards sensory words between post-treatment and follow-up were predicted by pre- to post- treatment changes in fear of movement (Tampa Scale for Kinesiophobia) but not other relevant variables, such as fear of pain or anxiety sensitivity. These results demonstrate that successful cognitive-behavioural treatments can reduce selective attention, thought to be indicative of hypervigilance towards pain. Moreover, these biases appear to be changed by reducing the fear associated with movement. Theoretically, these results provide support for the fear of (re)injury model of pain. Clinically, this study supports the contention that fear of (re)injury and movement is an appropriate target of pain management and that reducing these fears causes patients to attend less to pain-related stimuli.

<p>Fear among caregivers in mental health care has always existed. Fear is a basic feeling that will protect us from dangerous situations and it makes itself constantly reminded in the care of mentally ill patients. The feeling makes the carer distanced in the relationship. A distancemean consequences for the patient. When the caregiver don´t relieve the patients suffering, the health process stops and she remains in her suffering. The study is a qualitative literature review with latent content analysis of seven scientific articles. The results revealed three categories that describe the meaning of the caregivers fear and how it affects the caring relationship. The first category is about that caregivers is forced by their duty where it is found that caregivers, despite their fear, acts out of her duty as a constraint, or inside as a virtue. The second category includes the other's frightening world where caregivers is fear ofwhat is experienced as and incomprehensible. The third and final category is about mutual powerlessness where caregiver experience fear for the unpredictable and uncontrollable that can´t be foreseen. The powerlessness make the caregiver to question her professionalism andcompetence. The result showed that carers experienced fear of people with mental illness. Carers had difficulty understanding the patients life-world when it experienced incomprehensible and frightening. There was also fear in carers losing control and not to be sufficiently skilled in their profession. When the caregiver felt that she could not maintaincontrol, she was compelling in its approach to the patient and took the control to respond to her, witch affected the relationship negatively. It was found that caregivers were feared of being injured by patients. The results also showed that fear was making the caregiver rejective. This fear blocks the caring relationship. When the caregiver instead affirms her fearand accept it the conditions increase for the establishment of a caring relationship with the patient.</p>

Previous research indicates that serotonin (5-HT) enhances the acquisition of stress-induced changes in behavior; although it is unclear which serotonin receptors mediate this enhancement. 5-HT2 receptors are potential candidates because activation at these receptors is associated with increased fear and anxiety. In this study we investigated whether pharmacological treatments targeting 5-HT2A and 5-HT2C receptors modulated the acquisition and expression of conditioned defeat. Conditioned defeat is a social defeat model in Syrian hamsters (Mesocricetus auratus) that is characterized by increased submissive and defensive behavior and a loss of territorial aggression following social defeat. In experiment 1, we injected the 5-HT2C receptor agonist mCPP (0.3, 1.0, or 3.0 mg/kg) or vehicle prior to social defeat and tested subjects for conditioned defeat behavior in a social interaction test 24 hours later. In experiment 2, subjects received a social defeat, and 24 hours later we injected mCPP (0.3, 1.0, or 3.0 mg/kg) or vehicle prior to a social interaction test. We found that injection of mCPP increased the expression, but not acquisition, of conditioned defeat. In experiment 3, we injected the 5-HT2A receptor antagonist MDL 11,939 (0.5 or 2.0 mg/kg) or vehicle prior to a social defeat and tested subjects for conditioned defeat behavior. In experiment 4, subjects received a social defeat, and 24 hours later we injected MDL 11,939 (0.5 or 2.0 mg/kg) or vehicle prior to a social interaction test. We found that injection of MDL 11,939 significantly decreased the acquisition, but not expression, of conditioned defeat. These data suggest that pharmacological activation of 5-HT2C receptors enhances the expression of conditioned defeat, while pharmacological blockade of 5-HT2A receptors impairs the acquisition of conditioned defeat. These data extend other studies indicating that 5-HT signaling at 5-HT2A receptors facilitate memories for aversive events and 5-HT signaling at 5-HT2C receptors enhance stress-induced anxiety.