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.

In the present study, footshock, which produces a powerful aversive emotional response was used in a Pavlovian conditioning experiment as an unconditioned stimulis (UCS), and was paired with the presentation of a light used as a conditioned stimulis (CS). There is an accumulation of evidence that supports the assertion that dopaminergic (DA) neurons within the ventral tegmental area (VTA) are active in processes that contribute to the amygdala-based circuitry involved in regulating emotionally salient responses. To build upon findings implicating VTA DA, excitatory glutamate (Glu), NMDA and AMPA receptors, were examined with respect to their role in Pavlovian conditioned fear responding. Fear potentiated startle (FPS) was used to assess the effects of intra-VTA infused AP5, and intra-VTA infused CNQX on conditioned fear responding in laboratory rats. The administration of the NMDA receptor antagonist AP5 (at 1.0, 2.5, and 5.0ug doses), blocked the ability of a conditioned stimulus (CS) previously paired with footshock to become conditioned to the UCS. Similarly, administration of the AMPA receptor antagonist CNQX (at 1.0, 2.5, 5.0ug doses), inhibited the ability of the CS to become conditioned to the UCS. The results of this study indicate the VTA is an important site for synaptic modifications associated with fear learning, and that activation of excitatory Glutamatergic receptors in the VTA play a necessary part of the processing underlying fear conditioning. Measures of shock reactivity demonstrated that the infusion of AP5 and CNQX into the VTA did not inhibit baseline startle amplitudes. The administration of AP5 and CNQX did not suppress the perception of footshock as an aversive stimulus. This study provides further definition to established knowledge surrounding the neural processes whereby neutral environmental cues gain negative emotional salience as occurs in fear conditioning. It was hypothesised that the action of excitatory glutamatergic transmission within the VTA acts on NMDA and AMPA receptors is to assist in the acquisition of Pavlovian conditioned fear, possibly through the same synaptic mechanisms that govern LTP.

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.

Thesis (M.S.)--Georgia Southern University, 2007. / "A thesis submitted to the Graduate Faculty of Georgia Southern University in partial fulfillment of the requirements for the degree Master of Science." Under the direction of Jonathan N. Metzler. ETD. Electronic version approved: May 2007. Includes bibliographical references (p. 33-43) and appendices.

Diss. (sammanfattning) Stockholm : Karol. inst., 2003. / Härtill 4 uppsatser.

Diss. (sammanfattning) Örebro : Örebro universitet, 2007. / Härtill 5 uppsatser.

Thesis (M.Sc.)--University of Canterbury, 2007. / Typescript (photocopy). Includes bibliographical references (leaves 74-89). Also available via the World Wide Web.

Thesis (J.C.L.)--Catholic University of America, 1994. / Includes bibliographical references (leaves 57-63).

Thesis (Ph. D.)--Virginia Polytechnic Institute and State University, 1993. / Vita. Abstract. Includes bibliographical references (leaves 108-116). Also available via the Internet.

Dissertation (Ph.D.)--University of Toledo, 2008. / Typescript. "Submitted as partial fulfillment of the requirements for The Doctor of Philosophy degree in Psychology." Bibliography: leaves 77-86.