Interaction between 5-HT1B receptors and nitric oxide in zebrafish responses to novelty

AbstractNitric oxide (NO) and serotonin (5-HT) interact at the molecular and systems levels to control behavioral variables, including agression, fear, and reactions to novelty. In zebrafish, the 5-HT1B receptor has been implicated in anxiety and reactions to novelty, while the 5-HT1A receptor is associated with anxiety-like behavior; this role of the 5-HT1A receptor is mediated by NO. This work investigated whether NO also participates in the mediation of novelty responses by the 5-HT1B receptor. The 5-HT1B receptor inverse agonist SB 224,289 decreased bottom-dwelling and erratic swimming in zebrafish; the effects on bottom-dwelling, but not on erratic swimming, were blocked by pre-treatment with the nitric oxide synthase inhibitor L-NAME. These effects underline a novel mechanism by which 5-HT controls zebrafish reactivity to novel environments, with implications for the study of neotic reactions, exploratory behavior, and anxiety-like states

Behavioral and neurochemical changes in the zebrafish leopard strain

<p>Abstract</p> <p>The zebrafish leopard phenotype (leo) displays abnormal pigmentation and increased anxiety-like behavior. The neurochemical changes associated with this anxious phenotype are not known. Here, we demonstrate that leo show increased anxiety-like behavior in the light/dark box and in the novel tank test. This anxious phenotype is rescued by acute treatment with a dose of a serotonin reuptake inhibitor, fluoxetine, that is inactive in wild-type animals. Moreover, leoshow decreased tissue levels of serotonin, increased serotonin turnover, and slightly increased monoamine oxidase activity. These results suggest that the anxious phenotype observed in leo zebrafish is caused by a decrease in serotonin uptake.</p

Therapeutic concentration of morphine reduces oxidative stress in glioma cell line

Morphine is a potent analgesic opioid used extensively for pain treatment. During the last decade, global consumption grew more than 4-fold. However, molecular mechanisms elicited by morphine are not totally understood. Thus, a growing literature indicates that there are additional actions to the analgesic effect. Previous studies about morphine and oxidative stress are controversial and used concentrations outside the range of clinical practice. Therefore, in this study, we hypothesized that a therapeutic concentration of morphine (1 μM) would show a protective effect in a traditional model of oxidative stress. We exposed the C6 glioma cell line to hydrogen peroxide (H₂O₂) and/or morphine for 24 h and evaluated cell viability, lipid peroxidation, and levels of sulfhydryl groups (an indicator of the redox state of the cell). Morphine did not prevent the decrease in cell viability provoked by H₂O₂) but partially prevented lipid peroxidation caused by 0.0025% H₂O₂) (a concentration allowing more than 90% cell viability). Interestingly, this opioid did not alter the increased levels of sulfhydryl groups produced by exposure to 0.0025% H₂O₂), opening the possibility that alternative molecular mechanisms (a direct scavenging activity or the inhibition of NAPDH oxidase) may explain the protective effect registered in the lipid peroxidation assay. Our results demonstrate, for the first time, that morphine in usual analgesic doses may contribute to minimizing oxidative stress in cells of glial origin. This study supports the importance of employing concentrations similar to those used in clinical practice for a better approximation between experimental models and the clinical setting

Local inhibition of nitrergic activity in tenotomized rats accelerates muscle regeneration by increasing fiber area and decreasing central core lesions

Muscular atrophy is a progressive degeneration characterized by muscular proteolysis, loss of mass and decrease in fiber area. Tendon rupture induces muscular atrophy due to an intrinsic functional connection. Local inhibition of nitric oxide synthase (NOS) by No-nitro-L-arginine methyl ester (L-NAME) accelerates tendon histological recovery and induces functional improvement. Here we evaluate the effects of such local nitrergic inhibition on the pattern of soleus muscle regeneration after tenotomy. Adult male Wistar rats (240 to 280 g) were divided into four experimental groups: control (n=4), tenotomized (n=6), vehicle (n=6), and L-NAME (n=6). Muscular atrophy was induced by calcaneal tendon rupture in rats. Changes in muscle wet weight and total protein levels were determined by the Bradford method, and muscle fiber area and central core lesion (CCL) occurrence were evaluated by histochemical assays. Compared to tenotomized (69.3±22%) and vehicle groups (68.1%±17%), L-NAME treatment induced an increase in total protein level (108.3±21%) after 21 days post-injury. A reduction in fiber areas was observed in tenotomized (56.3±1.3%) and vehicle groups (53.9±3.9%). However, L-NAME treatment caused an increase in this parameter (69.3±1.6%). Such events were preceded by a remarkable reduction in the number of fibers with CCL in L-NAME-treated animals (12±2%), but not in tenotomized (21±2.5%) and vehicle groups (19.6±2.8%). Altogether, our data reveal that inhibition of tendon NOS contributed to the attenuation of atrophy and acceleration of muscle regeneration

Ação da fluoxetina e WAY100,635 nos processos neuroquímicos, ativação simpática e analgesia induzida pela substância de alarme em paulistinhas adultos (Danio rerio)

<p>Poster presented at SBnEC 2014</p

A3 adenosine receptors modulate behavior and serotonergic system in zebrafish: Mediation by the nitric oxide pathway

<p>Extracellular serotonin (5-HT) levels in the brain are thought to mediate many different behavioral functions, including anxiety and stress; the main mechanism to regulate extracellular 5-HT levels is through reuptake, which are regulated by a plethora of mechanisms. Here, we demonstrate that activation of A3 adenosine receptors by IB-MECA decreases scototaxis, geotaxis, neophobia and arousal in zebrafish in vivo, increases extracellular brain 5-HT levels ex vivo, and increases 5-HT uptake in vitro. The effects of IB-MECA on 5-HT uptake, on extracellular 5-HT concentrations and on scototaxis are dependent on L-type calcium channels, nitric oxide synthase, and serotonin transporters; the effects of IB-MECA on geotaxis, on the other hand, are dependent on nitric oxide synthase, but not on serotonin transporters or calcium channels. These results underline a potential target to control 5-HT uptake and its behavioral consequences.</p

Receptors A3A modulam o comportamento e o sistema serotonérgico no zebrafish: Mediação pela via do óxido nítrico

<p>Poster presented at 36th meeting from the Brazilian Neurosciences and Behavior Society</p

Análise das variáveis comportamentais em diferentes linhagens selvagens de zebrafish: Papel das monoaminas cerebrais

<p>Poster presented at the 36th Meeting of the Brazilian Society for Neurosciences and Behavior (SBnEC)</p