Thesis (Ph. D.)--University of Wyoming, 2007. / An interdisciplinary thesis in psychology and neuroscience. Title from PDF title page (viewed on Dec. 5, 2008). Includes bibliographical references.

Both chronic psychosocial stress and chronic administration of corticosterone have been shown to alter serotonergic type 2A (5-HT2A) receptor activity. A non-invasive behavioural index of 5-HT2A receptor activity is the frequency of "wet dog shakes" (WDS) or serotonergic stereotypy. In addition to WDS, 5-HT2A receptors mediate effects on sexual behaviour in the rat, in particular, inhibition in the male and stimulation in the female. In the present series of experiments, the potential involvement of stress and corticosterone in the regulation of WDS and sexual behaviour in the male and female rat was investigated. In Experiments 1-4, chronic exposure to several different forms of psychosocial stress was found to facilitate female and inhibit male rat sexual behaviour while concurrently increasing the display of WDS in both sexes. In Experiment 5, nefazodone, an antidepressant with 5-HT2A antagonistic properties, blocked the effects of stress on WDS but not sexual behaviour in female rats. In Experiments 6-7, the corticosterone synthesis inhibitor, metyrapone, blocked the effects of stress on sexual proceptivity and WDS in female rats. Metyrapone blocked the effects of stress on WDS but not sexual behaviour in male rats. In Experiments 8-9, high doses of corticosterone administered chronically facilitated female and inhibited male rat sexual behaviour while concurrently increasing WDS in both sexes. In Experiments 10-11, the 5-HT2A antagonist ketanserin was found to completely attenuate the effects of corticosterone on sexual behaviour and WDS in both male and female rats. In Experiments 12-13, the acute administration of corticosterone was found to exert no effect on either sexual behaviour or WDS in male or female rats. The present results indicate that both chronic corticosterone treatment and exposure to chronic stress inhibit male and facilitate female sexual behaviour while concurrently increasing WDS behaviour. The stress-induced facilitation of WDS appears to be related to elevated corticosterone levels and is suggestive of increased 5-HT2A activity. Both corticosterone and stress exerted effects on sexual behaviour in the direction that would be predicted by increased 5-HT2A activity. While the effects of corticosterone on sexual behaviour appear to be mediated by 5-HT2A activity, the effects of stress on sexual behaviour do not appear to be related to either elevations in corticosterone levels or alterations in 5-HT2A activity. / Arts, Faculty of / Psychology, Department of / Graduate

Depression is an extremely common, devastating psychiatric syndrome with profound effects on the structure of neurons and the proteins that they express. However, the pathophysiology of depression remains unclear despite decades of extensive research efforts, and this lack of understanding makes it difficult to develop effective treatments. It is extremely problematic that conventional antidepressant drugs do not work for many patients, and those that do respond require weeks to months of continuous treatment before adequate therapeutic improvement is achieved. Therefore, there is a clear unmet need to develop mechanistically novel antidepressant compounds that are well-tolerated, more effective, and faster acting. Subjecting rats to repeated-corticosterone (CORT; stress hormone analogous to cortisol for humans) injections produces a depressive-like phenotype that can be used to make inferences about the human condition and screen compounds for antidepressant properties. Our laboratory has previously found that stress downregulates hippocampal reelin in a similar manner to that seen in depression patients, and that drugs with antidepressant actions recover this deficit. This provided a rationale to administer reelin directly into the hippocampus, which rescued behavioral and neurochemical deficits, but intrahippocampal infusions are not clinically viable. Reelin is expressed in the periphery and blood as well as the brain, so the aims of the collection of studies described here are to evaluate the antidepressant-like properties of peripheral intravenous (i.v.) reelin. In the first experiment, the antidepressant-like effects of several dosages of reelin (3/5μg given every 5/10 days) were evaluated in rats that were exposed to 3-weeks of daily CORT (40mg/kg) injections. I found that all the dosages of reelin attenuated CORT-induced despair-like behavior in the forced-swim test (FST) and normalized alterations in serotonin (5-HT) transporter (SERT) membrane protein clustering (MPC) in blood lymphocytes. Reelin treatment also increased reelin-immunoreactive (IR) cell counts in the hippocampal dentate gyrus (DG) subgranular zone (SGZ), but it had less of an effect on neurogenesis as measured by the number and maturation rate of doublecortin (DCX)-IR cells. Interestingly, the lowest dosage used also rescued the number of reelin-IR cells in the hypothalamic paraventricular nucleus (PVN). This suggested that the restoration of SGZ-reelin plays a pivotal role in attenuating depressive-like behavior and that 3μg every 10 days was the most effective dosage that was tested. Using the lowest dosage that showed to be effective in the first experiment, I then evaluated if male and female rats responded similarly to i.v. reelin using a larger battery of behavioral tests. Post-mortem tissue analyses focused on reelin and receptors that bind gamma-aminobutyric acid (GABA) and glutamate in the SGZ, which have been implicated in psychiatric disorders and the mediation of fast-acting antidepressant responses. I found that reelin rescued the FST- behavioral and neurochemical alterations induced by CORT similarly in both sexes, indicating that it may have therapeutic effects by normalizing inhibitory/excitatory transmission. I also evaluated the effect of i.v. reelin on neurogenesis in females and found that, akin to males, the regulation of adult-born cells by peripheral reelin is unlikely to mediate the antidepressant-like effects. The goal of the third experiment was to examine whether the antidepressant-like effects of peripheral reelin are achieved in a rapid manner. I found that a single 3μg injection after 3 weeks of CORT significantly decreased behavioral deficits in the FST 24 hours later in both sexes. Reelin also partially rescued cognitive deficits and expression levels of reelin, GluN2B, and mitochondrial-related pro-apoptotic factors bcl-2 associated X protein (BAX) and cytochrome C (CytC) in the DG. In addition, a single injection of reelin fully recovered the number of GluA1-expressing cells and partially recovered SERT cluster size in males, whereas reelin partially recovered GluA1-IR cell counts and fully recovered SERT cluster sizes in females. Reelin had modest effects on DCX-IR cells in both sexes. The final chapter summarizes and discusses my findings, which suggest that the antidepressant-like effects of peripheral reelin are associated with the recovery of neurochemical deficits that strengthen neurotransmission, at least in the hippocampus. Therefore, developing reelin-based therapeutics with antidepressant activity would be a fruitful area of research, although additional mechanistic, pharmacokinetic, and pharmacodynamic studies are essential. / Graduate

No description available.

Stress is a physiological state induced by disturbance or adverse environmental conditions and is modulated by the glucocorticoid hormone corticosterone (CORT) in reptiles. Stressors can have various impacts on vertebrate trait expression and may affect survival or reproduction. Little is known about the effects of chronically elevated CORT in free-ranging reptiles, or the effect of disturbance stress on venom composition in captive snakes. In chapter 1, we investigated the effects of researcher induced disturbance on CORT levels and venom composition in a group of captive Northern Pacific rattlesnakes (Crotalus oreganus). Venom protein concentration and plasma CORT levels were compared before and after two weeks of unpredictable bouts of cage vibration, and to a non-vibrated control group. CORT levels were also assessed one week into vibration treatment. We found no effect of vibration treatment on CORT levels or on venom composition, and within-snake relative protein abundance was highly repeatable, although some variation was observed. We found a strong correlation between changes in relative abundance of several proteins and CORT. These results led us to believe that while differential forms of researcher-induced disturbance may not affect venom composition, significant changes in baseline CORT, or chronic stress, may affect the venom phenotype. In the next study, we investigated the effects of chronically elevated CORT in a wild population of radio-telemetered Southern Pacific rattlesnakes (C. helleri). Snakes were implanted intra-coelomically with either crystalline CORT or sham implants. Prior to implant and for two week periods thereafter, we sampled blood, venom, defensive behavior, and body temperature (Tb). Thermal data logger implants recorded snake Tb each hour. Snakes were tracked daily for one month, and detectability, defensive behavior, movement, home range size and thermal parameters were calculated for each group during the periods between samples. Stress reactivity was assessed as change in CORT from baseline after one hour of acute confinement stress. CORT implants led to elevated baseline CORT for at least two weeks in treatment snakes, showing that our treatment was successful. Chapter 2 describes the effects of CORT treatment on venom parameters. Increased baseline CORT was associated with increased activity of venom protein phospholipase A2, indicating that CORT may have direct effects on regulating venom protein activity. Overall, venom activity was repeatable within individual snakes. Chapter 3 describes the effect of CORT on behavioral, ecological, and physiological variables. Implant treatment led to decreased average Tb in weeks two and three. We detected a trend for lower baseline CORT to predict a greater magnitude of acute stress response. Snakes with higher testosterone levels exhibited higher defensive behavior scores. Overall, there were no other effects of implant treatment. Our results suggest that rattlesnake thermoregulation is impacted by chronic stress, which could affect other aspects of their metabolism and ecology. Results of both studies suggest baseline CORT may direct both the activity and relative abundance of venom proteins in different manners, a hypothesis which deserves further investigation using proteomic tools. When responding to an acute stressor, rattlesnakes may secrete CORT until a threshold response is reached, regardless of baseline levels. Overall, rattlesnakes appear resilient to the effects of researcher-induced disturbance in the laboratory and to two weeks of chronically elevated CORT in the field, as no change was detected in many of the parameters investigated.

No description available.

No description available.

No description available.

No description available.

Urban areas are a unique and growing habitat type. Animals living in this novel habitat are faced with new challenges, but may also encounter novel opportunities. Though urban animals have been observed to differ from their rural counterparts in a variety of behavioral and physiological traits, little is known about the specific features of urban areas that drive these differences and whether they are adaptive. Understanding this process is important from a conservation perspective and also to gain insight into how animals colonize novel habitats more generally. Using song sparrows (Melospiza melodia), a native songbird commonly found in urban areas, I explored responses to urbanization and the drivers and consequences of these responses with an eye toward understanding whether song sparrows had successfully adapted to urban habitats (Chapter I). I began by comparing body condition and levels of corticosterone, a hormone associated with energy management and the stress response in birds, between urban and rural populations (Chapter II). There was more variation across years than between habitats, suggesting that a variable environmental factor common to both habitats is the primary driver of these traits. I then compared territorial aggression levels and tested the effect of food availability on aggression (Chapter III). Fed rural birds and all urban birds had higher aggression levels than unfed rural birds, indicating that territorial aggression is related to resource availability in this species and that urban habitats may be perceived as more desirable. Finally, I looked for differences in reproductive timing and success and for relationships between reproductive success and aggression (Chapter IV). Higher reproductive success in urban populations, coupled with differences in the timing of successful nests between habitats, suggest differences in predation risk and predator community structure between habitats. In Chapter V, I synthesize my major findings and suggest directions for future research building on these results. I conclude that urban song sparrows differ from rural birds, that these differences are influenced by resource availability, and that urban habitats can potentially support stable song sparrow populations, though more research is necessary to determine the fitness impacts of specific traits that change with urbanization. / Ph. D.