A adolescência é um período crítico para o desenvolvimento dos indivíduos. Durante esta fase várias estruturas cerebrais responsáveis pelo controle das respostas estressoras atingem sua maturidade. Assim, estressores agudos ou crônicos podem repercutir negativamente e alterar a resposta de estresse bem como o comportamento na vida adulta. O eixo hipotálamo-hipófiseadrenal (HPA) integra o sistema do estresse, cujo controle inibitório está regulado pelos glicocorticoides, os quais agem em receptores dos tipos mineralocorticoide (MR) e glicocorticoide (GR). É desconhecido o papel destes receptores nos efeitos de longa duração induzidos pelo estresse na pré-puberdade em modelos animais. O objetivo deste trabalho foi verificar se o bloqueio dos receptores MR ou GR após o estresse na pré-puberdade previne suas alterações sobre o comportamento exploratório e o controle do eixo HPA, em ratas adultas. Desta forma, ratas pré-púberes, com 26 dias de idade, foram submetidas a uma ou sete sessões diárias de contenção e, em seguida, à administração dos antagonistas MR (Espironolactona) ou GR (RU- 486). Na fase adulta, aos 60 dias de idade, os animais foram avaliados no labirinto em cruz elevado e, no dia seguinte, submetidos novamente à contenção, concomitantemente com coleta seriada de sangue para avaliar a resposta do eixo HPA. Subsequentemente, realizou-se a perfusão do cérebro assim como a coleta das adrenais e timo. Efetuou-se a dosagem de corticosterona por radioimunoensaio e analisou-se a expressão e atividade dos neurônios CRH na região parvocelular medial do núcleo paraventricular do hipotálamo, por imuno-histoquímica. O estresse crônico na pré-puberdade causou redução no peso corporal, atraso na puberdade e diminuição da expressão de CRH e Fos em resposta ao estresse agudo na vida adulta. Não houve efeitos sobre o peso do timo e parâmetros comportamentais. Contudo, RU-486 promoveu aumento da corticosterona e adrenais. O estresse agudo ocasionou avanço da puberdade e associado com RU- 486 ou Espironolactona também diminuiu a atividade dos neurônios CRH em resposta ao mesmo estressor na vida adulta. Estes resultados demonstram que a administração de Espironolactona pode ser uma estratégia promissora para atenuar os efeitos centrais a longo prazo decorrentes do estresse agudo na pré-adolescência / Adolescence is a critical period to the individual\'s development. Several brain structures responsible for the control of stressful responses reach maturity during this phase. Thus, acute or chronic stressors can have a negative effect and alter the stress response as well as behavior in adulthood. The hypothalamus-pituitary-adrenal axis (HPA) is part of the stress system, whose inhibitory control is regulated by glucocorticoids through mineralocorticoid (MR) and glucocorticoid (GR) receptors. It is unknown the role of these receptors in the long-term effects induced by stress in the prepuberty in animals models. The aim of this study was determine whether MR or GR receptor blockade after stress in prepuberty prevents their changes on exploratory behavior and control of the HPA axis in adult female rats. Thus, prepuberty female rats, at 26 days old, were submitted to one or seven daily restraint sessions followed by administration of MR (Spironolactone) or GR (RU-486) antagonists. In adulthood, at 60 days old, the animals were evaluated in the elevated plus maze. In the next day, they were subject again to restraint concurrently with serial blood sampling to evaluate the HPA axis response. Subsequently, it was performed the brain perfusion as well as the collection of the adrenal glands and thymus. It was conducted the dosage of corticosterone by radioimmunoassay and analyzed the expression and activity of CRH neurons in the medial parvocellular subdivision of the paraventricular nucleus of the hypothalamus by immunohistochemistry. Chronic stress in prepuberty reduced the body weight, delayed the puberty and decreased the CRH and Fos expression in response to acute stress in adulthood. There was no effect on thymus weight and behavioral parameters. However, RU-486 increased the corticosterone secretion and adrenal glands weight. Acute stress caused advancement of puberty and associated with RU-486 or Spironolactone also reduced the activity of CRH neurons in response to the same stressor in adulthood. These results demonstrate that Spironolactone administration may be a promising strategy to attenuate the central long-term effects resulting from acute stress in prepuberty.

Sleep is a fundamental and essential component of vertebrate life, although its exact function remains unknown. Animals that are deprived of sleep typically show reduced neurobiological performance, health, and in some cases, survival. However, a number of animals exhibit adaptations that permit them to carry out normal activities even when sleep is restricted or deprived. Lapland longspurs (Calcarius lapponicus), arctic-breeding passerine birds, exhibit around-the-clock activity during their short breeding season, with an inactive period of only 3–4 h/day (71°N). Whether these birds suffer behavioral and physiological costs associated with acute sleep loss (SL) is unknown. To assess the effects of SL, wild-caught male longspurs were placed in captivity (12L:12D) and trained for 2 months using a series of memory tests, including color association and spatial learning to assess executive function. Birds were then placed in automated sleep fragmentation cages that utilize a moving wire to force movement every 1 min (60 arousals/h) during 12D (inactive period) or control conditions (during 12L; active period). After a single round of SL (or control) treatment, color association and spatial learning tests were conducted. Baseline plasma corticosterone concentration, body mass, and satiety were also assessed. SL significantly elevated corticosterone levels and increased accuracy during the color association test, but not the overall time required to complete the test. SL had no effect upon spatial learning, body mass, or satiety. Taken together, these results suggest that Lapland longspurs exhibit a behavioral, but not a physiological, resilience to acute SL.

A devastating feature of drug-dependence is the susceptibility of relapse (40-60%) after stretches of abstinence. One theory that may account for relapse suggests that drug cues (e.g., paraphernalia) may increase stress hormones, and this may prompt relapse. Repeatedly pairing a neutral cue with a reward is commonly utilized to measure what subjects learn about a cue that is predictive of reward. Research has shown that animals that attend to a cue more than to the reward (sign trackers) may be more vulnerable to drug addiction. Additionally, research has shown that sign tracking is associated with an increase in corticosterone (CORT), a primary stress hormone. PT 150 is a novel glucocorticoid receptor antagonist that attenuates the effects of CORT. Experiment 1 hypothesized that subjects given repeated oral administration of 40 mg/kg PT 150 would reduce sign tracking compared to subjects given placebo. Results of Experiment 1 showed that repeated oral consumption of 40 mg/kg PT 150 decreased sign tracking behavior compared to placebo. In Experiment 2, it was hypothesized that PT 150 (20/40/60 mg/kg) given by subcutaneous (SC) injection would reduce sign tracking dose-dependently, and that sign tracking behavior would correlate with CORT levels. Results of Experiment 2 showed that SC injection of 20 mg/kg PT 150 reduced sign tracking but not 40 or 60 mg/kg. Additionally, the correlation between CORT and the sign tracking for the 20 mg/kg approached significance. Although tentative, the correlation may suggest that elevated plasma CORT concentrations correlate with elevated sign tracking. The current findings extend the current literature by suggesting that the glucocorticoid receptor may be a potential pharmacological target for reducing relapse-like behaviors.

Stress has been shown to influence learning and memory in humans and rats (Diamond et al, 1996; Diamond et al, 1999; Krugers et al, 1997; Kirschbaum et al, 1996; Lupien et al, 1997). The hippocampus and is an area of the brain involved in memory function in humans and rats (Kirschbaum et al, 1996; Lupien et al, 1997) and is highly susceptible to stress (Diamond et al, 1990). Research has indicated that a number of stressors such as exposure to a predator (Diamond et al, 1999) can lead to stress effects. Recently efforts have been made to counteract the effects of stress on brain function and related behavioral performance. The antidepressant drug tianeptine has been used in this setting. Little is known about tianeptine's role in blocking stress effects on behavior and memory performance with regard to interactions with stress hormones, such as corticosterone. Here a set of experiments delineates the role of corticosterone and its link to stress effects on memory as well as an investigation into the actions of tianeptine and ADX in the blockade of stress effects on memory. First, I examined the effects of tianeptine on multi-day RAWM working memory training and a novel one-day learning and memory training task. Second, the effects of propranolol, an anti-anxiety medication, were tested with regard to the alleviation of stress effects on memory, allowing for a comparison between two anti-anxiety drugs, tianeptine and propranolol. Third, adrenalectomy (ADX) and the resultant depletion of adrenal hormones were examined in connection with learning and memory in the one-day learning task. Fourth, the effects and interactions of tianeptine and ADX were examined to see if tianeptine can exert its effects in the absence of adrenal hormones. Tianeptine blocked stress-induced memory errors in two different tasks and under ADX conditions. All effects were independent of corticosterone levels. In contrast, propranolol was ineffective in blocking stress-induced memory changes. The current data may prove useful in the development of antidepressant drugs and further the study of the mechanisms by which stress affects memory.

Some male sexually selected traits are sensitive to stressors early in life and provide females with information to discriminate among males with different developmental experiences. Moreover, female early life experiences could also impact which males they choose. Females might either choose honest traits indicative of male quality, no matter their own experiences, or they might choose mates to match or compensate for their own experiences. To determine how developmental stressors alter male sexually-selected traits and female preference thereof, I exposed zebra finches (Taeniopygia guttata, ZEFI) to i) lipopolysaccharide (LPS), an immunogenic, Gram-negative bacterial component, ii) corticosterone (CORT), an avian stress steroid, iii) both challenges (CORT/LPS), or iv) none of the above (control vehicles). Finches were exposed during development (12-28 days post-hatch) and male traits (e.g., body size, bill and cheek coloration) and female behaviors (e.g., general activity, male sampling effort, and male preference) were then measured in adulthood. Control males were predicted to express the most elaborate traits followed by LPS, CORT, and then CORT/LPS males. If female preference was generally driven by male quality, control females were predicted to be most selective followed by LPS, CORT, and CORT/LPS females. Alternatively, if female choice was contingent on her own experience, females might choose males with similar (i.e, matching) or distinct (i.e, complementarity) developmental histories. Of the male characteristics measured, only cheek coloration was impacted by treatment early in life; CORT/LPS males had duller, less orange cheeks than controls. For females, overall activity was reduced in CORT/LPS females. More importantly in regards to mate choice, females exhibited a blend of matching and complimentary behavior; females not exposed to LPS or CORT preferred males also not exposed to LPS or CORT. In general, females avoided LPS males no matter their own experience. Altogether, this study suggests that female mate preference is quite sensitive to early-life experiences and driven by a mix of choice of outright male quality and relative complementarity.

I conducted an integrative field study on male cottonmouths (Agkistrodon piscivorus), a common pitviper of the southeastern United States, to investigate the evolution of contrasting mating patterns in North American pitvipers (bimodal and unimodal annual patterns) and resolve conflicting information about the pattern exhibited by the cottonmouth. I determined a unimodal late summer peak of testosterone (T) and a muted unimodal seasonal cycle of the sexual segment of the kidney (a secondary sexual characteristic), both of which were correlated with the single peak of spermatogenesis in late summer. I also conducted a study to determine diel and seasonal variation of corticosterone (CORT), the effect of captive handling on CORT, and the relationship between CORT and T after captive handling, and detected a significant elevation of CORT and a significant decrease of T after capture in male cottonmouths, as well as a significant negative correlation between CORT and T.

Thesis (Ph. D.)--University of Hong Kong, 2009. / Includes bibliographical references (p. 200-224). Also available in print.

Thesis (Ph. D.)--University of Hong Kong, 2009. / Includes bibliographical references (p. 200-224). Also available online.

Not available / text

Not available / text