Pup directed maternal licking and grooming (LG) increases with corticosterone (CORT) supplimentation (Rees et al 2004). Increases in LG lead to an attenuation of the adult offspring's HPA response to stress (Liu et aI1997). Similarly, Neonatal increases in glucocorticoids lead, in adulthood, to the same attenuation of the HPA stress response (Catalani et aI1993). We hypothesize that dams exhibiting increased LG will have increased circulating CORT, and this increase will be reflected in their offspring. This thesis characterizes the HPA hormone profile adrenocorticotropic hormone (ACTH), CORT & Corticosterone Binding Globulin (CBG) in High LG (H) and Low LG (L) litters, 5 days postpartum (P4). Furthermore pup plasma CORT levels are determined at (P) 3,4,6,10 & 14. Finally P10 Hand L LG ACTH, CORT & CBG will be assessed after stress. RESULTS: H compared to L LG dams have significantly increased plasma CORT (p=0.03). At P4, H LG offspring have significantly increased plasma CORT (p=0.03) and significantly decreased plasma ACTH (p=0.04) as compared to L LG offspring. Plasma CBG levels are significantly lower in H compared to L LG offspring (p=0.01) at the same age. Across the Stress Hyporesponsive Period (SHRP) H LG offspring had significantly increased plasma CORT (p= 0.00) compared to L LG offspring at P3. Challenged with a stressor at P10, H LG offspring have an exaggerated plasma CORT response (p=0.00). This data suggests increases in plasma CORT in the dams leads to increased CORT in the high offspring, contributing perhaps to a more mature stress response at P10. / Key word abbreviation: (1) CORT - CORTicosterone, (2) ACTH - AdrenoCorticoTropin releasing Hormone, (3) CBG - Corticosteroid Binding Globulin, (4) SHRP - Stress Hypo-Responsive Period, (5) P - Post-natal day, (6) HPA - Hypothalamic-Pituitary-Adrenal, (7) LG - Licking/Grooming, (8) ADX/OVX - ADrenalectomized/OVarectomized.

Ecstasy é o nome popular do 3,4-metilenodioximetanfetamina (MDMA), uma droga de abuso utilizada por adultos jovens. Diversos relatos têm mostrado existência de correlações positivas entre o abuso do Ecstasy e o aparecimento de doenças infecciosas. Muitos estudos em modelos animais mostram que o MDMA induz alterações de imunidade inata e adquirida; entretanto pouco se sabe sobre os mecanismos pelos quais estes efeitos ocorrem. Desta forma, buscamos neste trabalho os mecanismos neuroimunes pelos quais o MDMA diminui a atividade de neutrófilos e altera a distribuição de leucócitos nos diferentes compartimentos imunes. Além disso, avaliamos se os efeitos induzidos pelo MDMA afetam a resposta a uma infecção experimental induzida por Listeria monocytogenes. Nossos resultados mostram que 60 minutos após a administração de MDMA na dose 10mg/kg, houve 1) diminuição do burst oxidativo de neutrófilos induzido por SAPI e PMA e, também, da porcentagem e da intensidade da fagocitose dos neutrófilos sanguíneos; 2) diminuição da celularidade total da medula óssea e aumento da mesma no baço, além de diminuição do peso relativo do baço; 3) aumento na porcentagem de neutrófilos e diminuição na porcentagem de linfócitos sanguíneos; e 4) diminuição da expressão de NFB de neutrófilos sanguíneos. O tratamento com metirapona ou RU-486 prévio ao tratamento com MDMA foi capaz de inibir 5) os efeitos observados em todos os parâmetros avaliados na diminuição da atividade de neutrófilos; 6) as alterações das porcentagens de neutrófilos e linfócitos sanguíneos e 7) a diminuição da expressão de NFB. Observamos, ainda, que o tratamento com 6-OHDA ou ICI-118,551 prévio ao tratamento com MDMA 8) não foram capazes de inibir os efeitos induzidos pelo MDMA na atividade de neutrófilos e na contagem diferencial de leucócitos sanguíneos; no entanto, 9) preveniram as alterações de celularidade induzidas por MDMA na medula óssea e no baço, e 10) a diminuição do peso relativo do baço. Por fim, observamos em um modelo de infecção experimental por LM que o MDMA 11) induziu mielosupressão (diminuição do CFU na medula óssea e aumento no baço); 12) diminuiu o número de leucócitos sanguíneos e a celularidade da medula óssea; 13) aumentou a celularidade do baço; 14) diminuiu a produção de citocinas pró-inflamatórias (IL-12p70, TNF, IFN-, IL-6) e quimiocina (MCP-1) nas primeiras 24 h; e 15) aumentou a produção das mesmas citocinas e quimiocina após 72 h da indução da infecção. Desta forma, concluímos que os efeitos induzidos pelo MDMA sobre a atividade de neutrófilos foram provavelmente mediados pela diminuição da expressão de NFB induzido pela ação da corticosterona e que a corticosterona, também está envolvida com as alterações na contagem diferencial de neutrófilos e linfócitos. As catecolaminas periféricas responderam pelas alterações na distribuição de leucócitos entre baço e medula óssea, e diminuição do peso relativo do baço. Além disso, o MDMA pode ser considerado uma droga imunossupressora visto que diminuiu a resistência a uma infecção por LM por mecanismos neuroimunes / Ecstasy is the popular name of 3,4-metylendioxymetamphetamine (MDMA), a drug of abuse mainly used by young adults. Several reports have shown the existence of a positive correlation between Ecstasy abuse and increased susceptibility to infectious diseases. Some studies using animal models report that MDMA induces alterations in both innate and adaptive immunity, however little is known about the mechanisms that generate such alterations. Therefore, we sought for neuroimmune mechanisms that could be involved in the previously reported decreasing on neutrophil activity and alteration in the leukocyte distribution. Moreover, we analyzed the host resistance to Listeria monocytogenes after MDMA treatment. We show that MDMA (10 mg/kg), 60 min after administration: 1) decreases SAPI and PMA-induced oxidative burst and percentage/intensity of phagocytosis of circulating neutrophils; 2) decreases bone marrow cellularity while increases it in the spleen, and also decreases spleen relative weight; 3) increases neutrophil percentage while decreases lymphocyte percentage in the blood; and 4) decreases NFB expression on circulating neutrophils. Metyrapone or RU-486 prior to MDMA treatment abrogates 5) the MDMA effects previously reported on neutrophil activity; 6) alterations in the percentage of circulating neutrophils and lymphocytes, and 7) decreasing of NFB expression. We also show that 6-OHDA or ICI-118,551 prior to MDMA treatment were not able to 8) abrogated the MDMA effects previously reported on neutrophil activity and blood leukocyte differential counts; nevertheless, 9) they abrogated the previously reported alterations on bone marrow and spleen cellularity, and 10) reduction on spleen relative weight. Finally, in a model of host resistance to Listeria monocytogenes we show that MDMA: 11) induces myelosuppression by decreasing CFU on bone marrow while increasing it on spleen; 12) decreases circulating leukocytes and bone marrow cellularity; 13) increases spleen cellularity; 14) decreases pro-inflammatory cytokines production (IL-12p70, TNF, IFN-, IL-6) and chemokine (MCP-1) after 24h of the infection; and 15) increases the production of the pro-inflammatory cytokines and chemokines previously reported after 72h of the infection. Thus, we conclude that the MDMA effects on neutrophil activity were mediated by the reduction of NFB expression, and this effect was induced by corticosterone elevation in the serum. Corticosterone is also involved in the alterations on neutrophil and lymphocyte counts. Catecholamines were shown to be involved in the alterations on leukocyte distribution in the bone marrow and spleen, and in the reduction of relative weight of spleen. Additionally, MDMA reduced the host resistance to Listeria monocytogenes. Therefore, MDMA can be considered an immunosuppressive drug and those effects are mediated by neuroimmune mechanisms

Hippocampal mineralocorticoid receptor mRNA expression was increased in male hamsters exposed to 18 days of short photoperiod relative to animals maintained under long day illumination (p < 0.05). Short day hamsters were also characterized by increased weight gain, and heavier adrenal glands (p < 0.05). The larger adrenals showed selective increases in the widths of the zonae reticularis and glomerulosa (p < 0.001). Incidences of torpor and reduced body temperature were observed in the short day animals. No changes were found in reproductive organ weights, systolic blood pressure, open-field behavior, or stress levels of plasma corticosteroids. We conclude that the hamster brain-adrenal axis responds rapidly to changes in photoperiod, raising the possibility that this axis is a primary mediator of shortened photoperiod responses.

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