Neuroendocrine, behavioral and macrophage activity changes induced by picrotoxin effects in mice.
The relevance and property of studies related to stress effects on immune function are undisputable. All studies conducted on stress-immune relationships, however, provide from physical and/or psychological stressors. Indeed, as far as it is of our knowledge brain-innate immune responses were not analyzed after anxiogenic-like drugs use. The present experiment was then undertaken to analyze the effects of picrotoxin (0.3, 0.6 and 1.0mg/kg doses) on behavior, macrophage activity, serum corticosterone and noradrenaline (NE) levels and turnover in the brain of adult mice. Results showed that picrotoxin treatment in mice: (1) decreased motor and rearing activities in an open-field; (2) decreased the number of entries into the plus-maze open-arms and decreased the time spent in the exploration of the plus-maze open-arms; (3) decreased both motor activity and the level of holes exploration in the hole-board; (4) increased the levels of serum corticosterone in dose-dependent way; (5) increased noradrenaline (NE) and MHPG levels and NE turnover in the hypothalamus; and (6) increased Staphylococcus aureus and PMA-induced macrophage oxidative burst. However, and contrary to that reported after physical or psychological stress, this drug induced no effects on macrophage phagocytosis and NE levels and turnover in the frontal cortex. The present results are thus showing that picrotoxin induces some but not all neuro-innate immunity changes previously reported for inescapable foot-shock and psychological stressors in mice. These facts suggest that this chemical stressor triggers CNS pathways that might be somehow different from those fired by inescapable foot-shock and psychological stressors, leading to different neuro-innate immune responses.
Stankevicius
D
D
Department of Pharmacology, Biomedical Sciences Institute, University of São Paulo, São Paulo, SP, Brazil.
Rodrigues-Costa
E C
EC
Camilo Flório
J
J
Palermo-Neto
J
J
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology; D001007:Anxiety / Q000523:psychology; D001522:Behavior, Animal / Q000187:drug effects*; D001923:Brain Chemistry / Q000187:drug effects; D003345:Corticosterone / Q000097:blood; D003975:Diazepam / Q000494:pharmacology; D005434:Flow Cytometry; D018756:GABA Antagonists / Q000494:pharmacology*; D007031:Hypothalamus / Q000187:drug effects / Q000502:physiology; D007113:Immunity, Innate / Q000187:drug effects; D016676:Macrophages, Alveolar / Q000187:drug effects*; D008734:Methoxyhydroxyphenylglycol / Q000378:metabolism; D051379:Mice; D009490:Neurosecretory Systems / Q000187:drug effects*; D009638:Norepinephrine / Q000378:metabolism; D010852:Picrotoxin / Q000494:pharmacology*; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D016897:Respiratory Burst / Q000187:drug effects; D013315:Stress, Psychological / Q000276:immunology / Q000523:psychology
D014151:Anti-Anxiety Agents; D003345:Corticosterone; D003975:Diazepam; D018756:GABA Antagonists; D008734:Methoxyhydroxyphenylglycol; D009638:Norepinephrine; D010852:Picrotoxin