NOC-9, a selective nitric oxide donor, induces flight reactions in the dorsolateral periaqueductal gray of rats by activating soluble guanylate cyclase

Previous studies have showed that SIN-1, a nitric oxide (NO) donor, injected into the dorsolateral column of the periaqueductal gray (dlPAG) induces flight reactions. This drug, however, can also produce peroxynitrite, which may interfere in this effect. In addition, it is also unknown if this effect is mediated by local activation of soluble guanylate cyclase (sGC). The aims of this study, therefore, were (1) to investigate if NOC-9 (6-(2-Hydroxy-1-methyl-2-nitrosohydrazino)-N-methyl-1-hexanamine), a NO donor that does not produce peroxynitrite, would produce flight reactions after intra-dlPAG administration similar to those induced by SIN-1; (2) to verify if these responses could be prevented by local injection of a selective guanylate cyclase inhibitor (ODQ). Male Wistar rats (n = 5-12) with cannulae aimed at the dlPAG received injections of TRIS (pH 10.0, 0.5 mu l), NOC-9 (75 and 150 nmol), saline or SIN-1 (200 nmol) and were placed in an open arena for 10 min. In a subsequent experiment animals (n = 7-8) were pretreated with ODQ (1 nmol/0.5 mu l) before receiving NOC-9 150 nmol. NOC-9 induced a significant dose-dependent increase in flight reactions in the first minute after injection (% of animals displaying flight: vehicle = 0%, NOC 75 = 67%. NOC 150 = 75%). SIN-1 had a similar effect (100% of animals showing flight) but the effects lasted longer (10 min) than those of NOC-9. The effect of NOC-9 (150 nmol) was prevented by pretreatment with ODQ (% of animals displaying flight: vehicle + NOC 150 = 71 %, ODQ + NOC 150 = 37%). The results suggest that NO donors injected into the dlPAG induce defensive responses that are not mediated by secondary peroxynitrite production. Moreover, they also indicate that these defensive responses depend on activation of local sGC. The data strengthen the proposal that NO can modulate defensive reactions in the dlPAG. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

Analysis and manipulation of the structure of odor plumes from a piezo-electric release system and measurements of upwind flight of male Almond Moths, Cadra cautella, to pheromone plumes

We investigated the plume structure of a piezo-electric sprayer system, set up to release ethanol in a wind tunnel, using a fast response mini-photoionizaton detector. We recorded the plume structure of four different piezo-sprayer configurations: the sprayer alone; with a 1.6-mm steel mesh shield; with a 3.2-mm steel mesh shield; and with a 5 cm circular upwind baffle. We measured a 12 × 12-mm core at the center of the plume, and both a horizontal and vertical cross-section of the plume, all at 100-, 200-, and 400-mm downwind of the odor source. Significant differences in plume structure were found among all configurations in terms of conditional relative mean concentration, intermittency, ratio of peak concentration to conditional mean concentration, and cross-sectional area of the plume. We then measured the flight responses of the almond moth, Cadra cautella, to odor plumes generated with the sprayer alone, and with the upwind baffle piezo-sprayer configuration, releasing a 13:1 ratio of (9Z,12E)-tetradecadienyl acetate and (Z)-9-tetradecenyl acetate diluted in ethanol at release rates of 1, 10, 100, and 1,000 pg/min. For each configuration, differences in pheromone release rate resulted in significant differences in the proportions of moths performing oriented flight and landing behaviors. Additionally, there were apparent differences in the moths’ behaviors between the two sprayer configurations, although this requires confirmation with further experiments. This study provides evidence that both pheromone concentration and plume structure affect moth orientation behavior and demonstrates that care is needed when setting up experiments that use a piezo-electric release system to ensure the optimal conditions for behavioral observations.

Ungulate behavioral responses to the heterogeneous road-network of a touristic protected area in Africa

Understanding how wildlife responds to road and traffic is essential for effective conservation. Yet, not many studies have evaluated how roads influence wildlife in protected areas, particularly within the large iconic African National Parks where tourism is mainly based on sightings from motorized vehicles with the consequent development and intense use of roads. To reduce this knowledge gap, we studied the behavioral response and local spatial distribution of impala Aepyceros melampus along the heterogeneous (with variation in road surface type and traffic intensity) road-network of Kruger National Park (KNP, South Africa). We surveyed different types of roads (paved and unpaved) recording the occurrence of flight responses among sighted impala and describing their local spatial distribution (in relation to the roads). We observed relatively few flight responses (19.5% of 118 observations), suggesting impalas could be partly habituated to vehicles in KNP. In addition, impala local distribution is apparently unaffected by unpaved roads, yet animals seem to avoid the close proximity of paved roads. Overall, our results suggest a negative, albeit small, effect of traffic intensity, and of presence of pavement on roads on the behavior of impala at KNP. Future studies would be necessary to understand how roads influence other species, but our results show that even within a protected area that has been well-visited for a long time, wildlife can still be affected by roads and traffic. This result has ecological (e.g., changes in spatial distribution of fauna) and management implications (e.g., challenges of facilitating wildlife sightings while minimizing disturbance) for protected areas where touristic activities are largely based on driving.

Differential role of CB1 and TRPV1 receptors on anandamide modulation of defensive responses induced by nitric oxide in the dorsolateral periaqueductal gray

CB1, TRPV1 and NO can regulate glutamate release and modify defensive behaviors in regions related to defensive behavior such as the dorsolateral periaqueductal gray (dIPAG). A possible interaction between the endocannabinoid and nitrergic systems in this area, however, has not been investigated yet. The objective of the present work was to verify if activation of CB1 or TRPV1 receptors could interfere in the flight responses induced in rats by the injection of SIN-1, an NO donor, into the dIPAG. The results showed that local administration of a low dose (5 pmol) of anandamide (AEA) attenuated the flight responses, measured by the total distance moved and maximum speed in an open arena, induced by intra-dIPAG microinjection of SIN-1 (150 nmol). URB597 (0.1 nmol), an inhibitor of anandamide metabolism, produced similar effects. When animals were locally treated with the CB1 receptor antagonist AM251 the effective AEA dose (5 pmol) increased, rather than decreased, the flight reactions induced by SIN1-1. Higher (50-200 nmol) doses of AEA were ineffective and even tended to potentiate the SIN-1 effect. The TRPV1 antagonist capsazepine (CPZ, 30 nmol) prevented SIN-1 effects and attenuated the potentiation of its effect by the higher (200 nmol) AEA dose. The results indicate that AEA can modulate in a dual way the pro-aversive effects of NO in the dIPAG by activating CB1 or TRPV1 receptors. (C) 2012 Elsevier Ltd. All rights reserved.

Serotonergic modulation of face-emotion recognition

Facial expressions of basic emotions have been widely used to investigate the neural substrates of emotion processing, but little is known about the exact meaning of subjective changes provoked by perceiving facial expressions. Our assumption was that fearful faces would be related to the processing of potential threats, whereas angry faces would be related to the processing of proximal threats. Experimental studies have suggested that serotonin modulates the brain processes underlying defensive responses to environmental threats, facilitating risk assessment behavior elicited by potential threats and inhibiting fight or flight responses to proximal threats. In order to test these predictions about the relationship between fearful and angry faces and defensive behaviors, we carried out a review of the literature about the effects of pharmacological probes that affect 5-HT-mediated neurotransmission on the perception of emotional faces. The hypothesis that angry faces would be processed as a proximal threat and that, as a consequence, their recognition would be impaired by an increase in 5-HT function was not supported by the results reviewed. In contrast, most of the studies that evaluated the behavioral effects of serotonin challenges showed that increased 5-HT neurotransmission facilitates the recognition of fearful faces, whereas its decrease impairs the same performance. These results agree with the hypothesis that fearful faces are processed as potential threats and that 5-HT enhances this brain processing.

Stay out (almost) all night: contrasting responses in flight activity among tropical moth assemblages

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Fight versus flight: the interaction of temperature and body size determines antipredator behaviour in tegu lizards

Ectotherm antipredator behaviour might be strongly affected both by body temperature and size: when environmental temperatures do not favour maximal locomotor performance, large individuals may confront predators, whereas small animals may flee, simply because they have no other option. However, integration of body size and temperature effects is rarely approached in the study of antipredator behaviour in vertebrate ectotherms. In the present study we investigated whether temperature affects antipredator responses of tegu lizards, Tupinambis merianae, with distinct body sizes, testing the hypothesis that small tegus (juveniles) run away from predators regardless of the environmental temperature, because defensive aggression may not be an effective predator deterrent, whereas adults, which are larger, use aggressive defence at low temperatures, when running performance might be suboptimal. We recorded responses of juvenile (small) and adult (large) tegu lizards to a simulated predatory attack at five environmental temperatures in the laboratory. Most differences between the two size classes were observed at low temperatures: large tegus were more aggressive overall than were small tegus at all temperatures tested, but at lower temperatures, the small lizards often used escape responses whereas the large ones either adopted a defensive posture or remained inactive. These results provide strong evidence that body size and temperature affect the antipredator responses of vertebrate ectotherms. We discuss the complex and intricate network of evolutionary and ecological parameters that are likely to be involved in the evolution of such interactions. (C) 2009 The Association for the Study of Animal Behaviour. Published by Elsevier Ltd. All rights reserved.

Defensive responses to threat scenarios in Brazilians reproduce the pattern of Hawaiian Americans and non-human mammals

A former study with scenarios conducted in Hawaii has suggested that humans share with non-human mammals the same basic defensive strategies - risk assessment, freezing, defensive threat, defensive attack, and flight. The selection of the most adaptive strategy is strongly influenced by features of the threat stimulus - magnitude, escapability, distance, ambiguity, and availability of a hiding place. Aiming at verifying if these strategies would be consistent in a different culture, 12 defensive scenarios were translated into Portuguese and adapted to the Brazilian culture. The sample consisted of male and female undergraduate students divided into two groups: 76 students, who evaluated the five dimensions of each scenario and 248 medical students, who chose the most likely response for each scenario. In agreement with the findings from studies of non-human mammal species, the scenarios were able to elicit different defensive behavioral responses, depending on features of the threat. "Flight" was chosen as the most likely response in scenarios evaluated as an unambiguous and intense threat, but with an available route of escape, whereas "attack" was chosen in an unambiguous, intense and close dangerous situation without an escape route. Less urgent behaviors, such as "check out", were chosen in scenarios evaluated as less intense, more distant and more ambiguous. Moreover, the results from the Brazilian sample were similar to the results obtained in the original study with Hawaiian students. These data suggest that a basic repertoire of defensive strategies is conserved along the mammalian evolution because they share similar functional benefits in maintaining fitness.

The dorsal raphe nucleus exerts opposed control on generalized anxiety and panic-related defensive responses in rats

It has been proposed that the ascending dorsal raphe (DR)-serotonergic (5-HT) pathway facilitates conditioned avoidance responses to potential or distal threat, while the DR-periventricular 5-HT pathway inhibits unconditioned flight reactions to proximal danger. Dysfunction on these pathways would be, respectively, related to generalized anxiety (GAD) and panic disorder (PD). To investigate this hypothesis, we microinjected into the rat DR the benzodiazepine inverse receptor agonist FG 7142, the 5-HT1A receptor agonist 8-OH-DPAT or the GABA(A) receptor agonist muscimol. Animals were evaluated in the elevated T-maze (ETM) and light/dark transition test. These models generate defensive responses that have been related to GAD and PD. Experiments were also conducted in the ETM 14 days after the selective lesion of DR serotonergic neurons by 5,7-dihydroxytriptamine (DHT). In all cases, rats were pre-exposed to one of the open arms of the ETM 1 day before testing. The results showed that FG 7142 facilitated inhibitory avoidance, an anxiogenic effect, while impairing one-way escape, an anxiolytic effect. 8-OH-DPAT, muscimol, and 5,7-DHT-induced lesions acted in the opposite direction, impairing inhibitory avoidance while facilitating one-way escape from the open arm. In the light/dark transition, 8-OH-DPAT and muscimol increased the time spent in the lighted compartment, an anxiolytic effect. The data supports the view that distinct DR-5-HT pathways regulate neural mechanisms underlying GAD and PD. (C) 2002 Elsevier B.V. B.V. All rights reserved.

Physical environment modulates the behavioral responses induced by chemical stimulation of dorsal periaqueductal gray in mice

In order to investigate the relationship between behaviors elicited by chemical stimulation of the dorsal periaqueductal gray (dorsal PAG) and spontaneous defensive behaviors to a predator, the excitatory amino acid D,L-homocysteic acid (5 nmol in 0.1 mu l), was infused into the dorsal PAG and behavioral responses of mice were evaluated in two different situations, a rectangular novel chamber or the Mouse Defense Test Battery (MDTB) apparatus. During a 1-min period following drug infusion, more jumps were made in the chamber than in the MDTB runway but running time and distance traveled were significantly higher in the runway. Animals were subsequently tested using the standard MDTB procedure (anti-predator avoidance, chase and defensive threat/attack). No drug effects on these measures were significant. In a further test in the MDTB apparatus, the pathway of the mouse during peak locomotion response was blocked 3 times by the predator stimulus (anesthetized rat) to determine if the mouse would avoid contact. Ninety percent of D,L-homocysteic treated animals made direct contact with the stimulus (rat), indicating that D,L-homocysteic-induced running is not guided by relevant (here, threat) stimuli. These results indicate that running as opposed to jumping is the primary response in mice injected with D,L-homocysteic into the dorsal PAG when the environment enables flight. However, the lack of responsivity to the predator during peak locomotion suggests that D,L-homocysteic-stimulation into the dorsal PAG does not induce normal antipredator flight. (c) 2006 Published by Elsevier B.V.

Fight versus flight: the interaction of temperature and body size determines antipredator behaviour in tegu lizards

Ectotherm antipredator behaviour might be strongly affected both by body temperature and size: when environmental temperatures do not favour maximal locomotor performance, large individuals may confront predators, whereas small animals may flee, simply because they have no other option. However, integration of body size and temperature effects is rarely approached in the study of antipredator behaviour in vertebrate ectotherms. In the present study we investigated whether temperature affects antipredator responses of tegu lizards, Tupinambis merianae, with distinct body sizes, testing the hypothesis that small tegus (juveniles) run away from predators regardless of the environmental temperature, because defensive aggression may not be an effective predator deterrent, whereas adults, which are larger, use aggressive defence at low temperatures, when running performance might be suboptimal. We recorded responses of juvenile (small) and adult (large) tegu lizards to a simulated predatory attack at five environmental temperatures in the laboratory. Most differences between the two size classes were observed at low temperatures: large tegus were more aggressive overall than were small tegus at all temperatures tested, but at lower temperatures, the small lizards often used escape responses whereas the large ones either adopted a defensive posture or remained inactive. These results provide strong evidence that body size and temperature affect the antipredator responses of vertebrate ectotherms. We discuss the complex and intricate network of evolutionary and ecological parameters that are likely to be involved in the evolution of such interactions. (C) 2009 The Association for the Study of Animal Behaviour. Published by Elsevier Ltd. All rights reserved.

Criteria for acceptable representation of airplane dynamic responses in simulators used for pilot training.

"Contract no. N61339-1146."

Drosophila Flight Stabilization Depends on Apparent Distances in Optic Flow Field

To perform daily flight tasks, insects rely heavily on their visual perception of a dynamic environment. They must process visual signals quickly and accurately and update their behavior. Flies are vulnerable to environmental disturbances, such as gusts of wind blowing them off course, but they may use the altered visual field to compensate and regain their original course. In studies using Drosophila melanogaster, it has been shown that their corrective responses can be analyzed by measuring changes in their wing beats. By enclosing a tethered fly in a cuboidal visual arena displaying a computerized optic flow field, it is possible to calculate the change in wing beat amplitudes from an infrared shadow of its wings using photodiodes and a custom wing beat analyzer. In this experiment, manipulations ofthe optic flow field are used to create a field where points have varying relative forward speed, to study how the insect performs corrective maneuvers. The results show that Drosophila have a stronger corrective response to the quickly moving, apparently near points compared to the slower moving, apparently distant points. This implies the flies are distinguishing points based on their relative speeds, inferring distance, and adjusting their corrective actions with this information.

EFFECTS OF A VISUAL HORIZON ON DROSOPHILA MELANOGASTER OBJECT-TRACKING RESPONSES

To navigate effectively in three-dimensional space, flying insects must approximate distances to nearby objects. Humans are able to use an array of cues to guide depth perception in the visual world. However, some of these cues are not available to insects that are constrained by their rigid eyes and relatively small body size. Flying fruit flies can use motion parallax to gauge the distance of nearby objects, but using this cue becomes a less effective strategy as objects become more remote. Humans are able to infer depth across far distances by comparing the angular distance of an object to the horizon. This study tested if flying fruit flies, like humans, use the relative position of the horizon as a depth cue. Fruit flies in tethered flight were stimulated with a virtual environment that displayed vertical bars of varying elevation relative to a horizon, and their tracking responses were recorded. This study showed that tracking responses of the flies were strongly increased by reducing the apparent elevation of the bar against the horizon, indicating that fruit flies may be able to assess the distance of far off objects in the natural world by comparing them against a visual horizon.

Antiangiogenic And Finasteride Therapies: Responses Of The Prostate Microenvironment In Elderly Mice.

The aim of this study was to evaluate the structural and molecular effects of antiangiogenic therapies and finasteride on the ventral prostate of senile mice. 90 male FVB mice were divided into: Young (18 weeks old) and senile (52 weeks old) groups; finasteride group: finasteride (20mg/kg); SU5416 group: SU5416 (6 mg/kg); TNP-470 group: TNP-470 (15 mg/kg,) and SU5416+TNP-470 group: similar to the SU5416 and TNP-470 groups. After 21 days, prostate ventral lobes were collected for morphological, immunohistochemical and Western blotting analyses. The results demonstrated atrophy, occasional proliferative lesions and inflammatory cells in the prostate during senescence, which were interrupted and/or blocked by treatment with antiangiogenic drugs and finasteride. Decreased AR and endostatin reactivities, and an increase for ER-α, ER-β and VEGF, were seen in the senile group. Decreased VEGF and ER-α reactivities and increased ER-β reactivity were verified in the finasteride, SU5416 groups and especially in SU5416+TNP-470 group. The TNP-470 group showed reduced AR and ER-β protein levels. The senescence favored the occurrence of structural and/or molecular alterations suggesting the onset of malignant lesions, due to the imbalance in the signaling between the epithelium and stroma. The SU5416+TNP-470 treatment was more effective in maintaining the structural, hormonal and angiogenic factor balance in the prostate during senescence, highlighting the signaling of antiproliferation via ER-β.