Thesis advisor: Gorica D. Petrovich / Thesis advisor: Christina Reppucci / We are interested in exploring the instances in which environmental controls can override physiologic or homeostatic cues, and additionally the areas of the brain that might be implicated in such behavioral effects. For this study, we replicated a previously established behavioral finding in which male and female rats show fear-cue induced inhibition of eating, and that female rats take longer than male rats to extinguish this behavior. We assessed brain activation via Fos-expression in the NTS and DMX in the brainstem and found that males had higher brainstem activation than females during extinction of fear-cue induced inhibition of eating. Additionally, female experimental rats had suppressed activity in the caudal NTS compared to female control rats. The data from this study support our hypotheses that there are distinct activation patterns in the brainstem during the extinguishing of inhibition of eating, and that there are sex differences in these activation patterns. / Thesis (BS) — Boston College, 2013. / Submitted to: Boston College. College of Arts and Sciences. / Discipline: Psychology Honors Program. / Discipline: Psychology.

Thesis advisor: Gorica Petrovich / Thesis advisor: Christina Reppucci / In order to understand the neurobiological basis for the phenomenon in which environmental cues override physiological cues to influence the behavioral control of feeding, we utilized an animal model for fear-cue induced inhibition of eating. Female rats that had learned to associate a tone with foot-shocks showed inhibition of eating across three extinction tests, whereas male rats that had received tone-shock pairings extinguished their inhibition of eating after the first test day. We assessed activation of orexin (ORX), a neuropeptide involved in eating and arousal, in the lateral hypothalamic area (LHA) of the brains of male and female control and experimental rats during the final test day. Female rats exhibited greater recruitment of ORX neurons in the LHA than male rats; there was no difference in ORX activation between control and experimental groups of either sex, indicating that ORX is involved in sex differences in fear-cue induced inhibition of eating. / Thesis (BS) — Boston College, 2013. / Submitted to: Boston College. College of Arts and Sciences. / Discipline: College Honors Program. / Discipline: Psychology.

N-methyl-D-asparate (NMDA) receptors located within the basolateral complex of the amygdala are required for the consolidation and expression of Pavlovian conditioned fear. The events downstream of receptor activation that mediate these processes are not well defined. An intermediate step that may be of significance is the synthesis of the gas nitric oxide (NO). Nitric oxide is synthesised as a result of NMDA receptor activation and acts as an unconventional neurotransmitter freely diffusing across cell membranes interacting with its targets in a non-synaptic manner. The targets of NO include cellular components that play significant roles during the consolidation of conditioned fear and the neurotransmission associated with its expression. This implies that NO may be an important intermediary of NMDA receptor activation and both these processes. The current study sought to examine this possibility using fear potentiated startle to examine the expression of learned fear. Three experiments were conducted, fifty rats received intra-BSC microinfusions of the global nitric oxide synthase inhibitor L-NAME either prior to fear conditioning, fear testing, or examination of the shock sensitization of the acoustic startle affect. The results indicated that NO was indeed required for both the consolidation and expression of learned fear, whereas it was not required for shock enhanced startle responding. This study provides new information about the sub-cellular basis of conditioned fear, and highlights the pivotal role played by NO in processes associated with conditioned fear.

Posttraumatic Stress Disorder (PTSD) is an anxiety disorder that affects over 7.7 million adults and carries an estimated societal cost of $3.1 billion every year. People develop PTSD after exposure to a traumatic event. Alone or combined, approved pharmacotherapies or psychotherapy are somewhat effective, but symptoms for many remain refractory. Emerging evidence suggests that opiate systems may modulate the development and expression of PTSD, and their role can be investigated preclinically. Pavlovian fear conditioning is a preclinical model which elicits behaviors mirroring those that occur in humans during and after exposure to trauma. This presents an experimental tool that can help elucidate the opiate mechanisms involved in traumatic memory as well as the resulting fear behavior. Mu opioid receptor (MOR) analgesics, such as morphine, are often given as a response to trauma, and there is emerging evidence that they are, at least partially, protective against PTSD. The kappa opioid receptor (KOR) system has also been implicated in stress-related processes, with KOR agonists reported to enhance stress in both laboratory animals and in humans, and KOR antagonists reported to attenuate stress-like behaviors preclinically. This project attempted to clarify part of the role of the mu and kappa opiate receptor systems in mediating effects of Pavlovian fear conditioning in mice as a predictor of their involvement in some of the signs and symptoms of PTSD. Kappa agonists increased acute fear responses but surprisingly also facilitated fear extinction learning. This would suggest that the use of kappa agonists might increase the efficiency and effectiveness of this therapy and could improve existing PTSD patient outcomes. MOR agonists, as well as KOR antagonists reduced acute and long-term fear behavior. These results support that the use KOR analgesics like morphine and fentanyl in the treatment of trauma could have an added benefit of reducing the emergence and persistence of PTSD. Self-medication may help explain the comorbidity of opioid abuse in PTSD patient populations. Understanding the relative effects of these opiate ligands could lead to more informed usage of MOR analgesics which vary in mu and kappa receptor activity under battlefield and other traumatic conditions.

Thesis advisor: Gorica Petrovich / Thesis advisor: Christina Reppucci / Previously our lab has shown that food-deprived male and female rats will inhibit food consumption when presented with a conditioned stimulus that signals danger, and that this effect persists much longer in females than in males. The current experiment is part of a larger study that has two aims: 1) delineate the brain areas associated with fear-cue induced anorexia and 2) determine whether there are sex-differences in brain activation patterns. Female rats previously conditioned in an aversive paradigm inhibited food intake compared to female rats in the control group during three extinction tests, while experimental males only inhibited intake compared to male controls during test one. Following the third test, rats were sacrificed and brain tissue processed to assess activation patterns via Fos-expression within the central nucleus of the amygdala (CEA). We found that males had higher activation than females during test 3 in the CEA. / Thesis (BS) — Boston College, 2013. / Submitted to: Boston College. College of Arts and Sciences. / Discipline: Psychology Honors Program. / Discipline: Psychology.

N-methyl-D-asparate (NMDA) receptors located within the basolateral complex of the amygdala are required for the consolidation and expression of Pavlovian conditioned fear. The events downstream of receptor activation that mediate these processes are not well defined. An intermediate step that may be of significance is the synthesis of the gas nitric oxide (NO). Nitric oxide is synthesised as a result of NMDA receptor activation and acts as an unconventional neurotransmitter freely diffusing across cell membranes interacting with its targets in a non-synaptic manner. The targets of NO include cellular components that play significant roles during the consolidation of conditioned fear and the neurotransmission associated with its expression. This implies that NO may be an important intermediary of NMDA receptor activation and both these processes. The current study sought to examine this possibility using fear potentiated startle to examine the expression of learned fear. Three experiments were conducted, fifty rats received intra-BSC microinfusions of the global nitric oxide synthase inhibitor L-NAME either prior to fear conditioning, fear testing, or examination of the shock sensitization of the acoustic startle affect. The results indicated that NO was indeed required for both the consolidation and expression of learned fear, whereas it was not required for shock enhanced startle responding. This study provides new information about the sub-cellular basis of conditioned fear, and highlights the pivotal role played by NO in processes associated with conditioned fear.