Natural Aversive Stimuli Research Articles

Predatory Odor Exposure as a Potential Paradigm for Studying Emotional Modulation of Memory Consolidation-The Role of the Noradrenergic Transmission in the Basolateral Amygdala.

The pivotal role of the basolateral amygdala (BLA) in the emotional modulation of hippocampal plasticity and memory consolidation is well-established. Specifically, multiple studies have demonstrated that the activation of the noradrenergic (NA) system within the BLA governs these modulatory effects. However, most current evidence has been obtained by direct infusion of synthetic NA or beta-adrenergic agonists. In the present study, we aimed to investigate the effect of endogenous NA release in the BLA, induced by a natural aversive stimulus (coyote urine), on memory consolidation for a low-arousing, hippocampal-dependent task. Our experiments combined a weak object location task (OLT) version with subsequent mild predator odor exposure (POE). To investigate the role of endogenous NA in the BLA in memory modulation, a subset of the animals (Wistar rats) was treated with the non-selective beta-blocker propranolol at the end of the behavioral procedures. Hippocampal tissue was collected 90 min after drug infusion or after the OLT test, which was performed 24 h later. We used the obtained samples to estimate the levels of phosphorylated CREB (pCREB) and activity-regulated cytoskeleton-associated protein (Arc)-two molecular markers of experience-dependent changes in neuronal activity. The result suggests that POE has the potential to become a valuable behavioral paradigm for studying the interaction between BLA and the hippocampus in memory prioritization and selectivity.

Stressed rats fail to exhibit avoidance reactions to innately aversive social calls.

Disruptions in amygdalar function, a brain area involved in encoding emotionally salient information, has been implicated in stress-related affective disorders. Earlier animal studies on the behavioral consequences of stress-induced abnormalities in the amygdala focused on learned behaviors using fear conditioning paradigms. If and how stress affects unconditioned, innate fear responses to ethologically natural aversive stimuli remains unexplored. Hence, we subjected rats to aversive ultrasonic vocalization calls emitted on one end of a linear track. Unstressed control rats exhibited a robust avoidance response by spending more time away from the source of the playback calls. Unexpectedly, prior exposure to chronic immobilization stress prevented this avoidance reaction, rather than enhancing it. Further, this stress-induced impairment extended to other innately aversive stimuli, such as white noise and electric shock in an inhibitory avoidance task. However, conditioned fear responses were enhanced by the same stress. Inactivation of the basolateral amygdala (BLA) in control rats prevented this avoidance reaction evoked by the playback. Consistent with this, analysis of the immediate early gene cFos revealed higher activity in the BLA of control, but not stressed rats, after exposure to the playback. Further, in vivo recordings in freely behaving control rats exposed to playback showed enhanced theta activity in the BLA, which also was absent in stressed rats. These findings offer a new framework for studying stress-induced alterations in amygdala-dependent maladaptive responses to more naturally threatening and emotionally relevant social stimuli. The divergent impact of stress on defensive responses--impaired avoidance responses together with increased conditioned fear--also has important implications for models of learned helplessness and depression.

Eat or be eaten? Modifications of Aplysia californica feeding behaviour in response to natural aversive stimuli

Prey often modify their behaviours to diminish predation risk, but the persistence of such behavioural changes are not well understood. We investigated the effects of predation risk in the aquatic mollusc Aplysia californica to determine whether various natural aversive stimuli alter the expression of feeding behaviour (i.e. bites) over short-term (15 min), intermediate-term (2 h) and long-term (24 h) periods. Aplysia were presented with a variety of natural aversive stimuli that are indicative of predation risk, including exposure to the spiny lobster Panulirus interruptus (a natural predator), the blue crab Callinectes sapidus (a novel predator), and the defensive secretions ink and opaline that are normally released by Aplysia when attacked. Feeding was significantly suppressed immediately after Aplysia were exposed to ink but not to opaline. Additionally, several stimuli, including exposure to lobsters, ink, opaline and attacks from crabs, suppressed feeding, but only for a short time (i.e. 15 min) after the end of the stimulus. No single-exposure treatment elicited intermediate (2 h) or long-term (24 h) changes in feeding, and multiple exposures to ink did not induce long-term feeding suppression. Thus, changes in feeding behaviour in response to predation risk cues appear short-lived in Aplysia, unlike feeding suppression after electric shocks that suppress biting behaviour over longer periods. Since Aplysia possess chemical defences to defend against consumers, it is perhaps unnecessary or too costly to maintain feeding suppression after risk subsides.

Learning from others to cope with biting flies: Social learning of fear-induced conditioned analgesia and active avoidance.

Although fear conditioning has received extensive attention, little is known about the roles of social learning whereby an individual may learn and acquire the fear responses of another. The authors examined individually and socially mediated acquisition of fear and analgesia to the natural aversive stimulus of biting flies. Exposure to biting flies elicited in individual naive mice analgesia and active self-burying to avoid the flies. When exposed 24 hr later to flies whose biting parts were removed, but not to nonbiting house flies, these mice displayed conditioned analgesia and self-burying. This "one-trial" conditioned analgesia and avoidance was also acquired through social learning without direct individual experience with biting flies. Naive "observer" mice that witnessed other "demonstrator" mice being attacked by biting flies exhibited analgesia and self-burying 24 hr later to altered flies.

Decreased GABAA-receptor clustering results in enhanced anxiety and a bias for threat cues.

Patients with panic disorders show a deficit of GABAA receptors in the hippocampus, parahippocampus and orbitofrontal cortex. Synaptic clustering of GABAA receptors in mice heterozygous for the gamma2 subunit was reduced, mainly in hippocampus and cerebral cortex. The gamma2 +/- mice showed enhanced behavioral inhibition toward natural aversive stimuli and heightened responsiveness in trace fear conditioning and ambiguous cue discrimination learning. Implicit and spatial memory as well as long-term potentiation in hippocampus were unchanged. Thus gamma2 +/- mice represent a model of anxiety characterized by harm avoidance behavior and an explicit memory bias for threat cues, resulting in heightened sensitivity to negative associations. This model implicates GABAA-receptor dysfunction in patients as a causal predisposition to anxiety disorders.

Learning to cope with biting flies: Rapid NMDA-mediated acquisition of conditioned analgesia.

A 30-min exposure to intact biting flies (stable flies) induced an opioid-mediated analgesia in fly-naive male deer mice, whereas exposure to either altered biting flies whose biting mouthparts were removed or nonbiting house flies had no significant effects. However, mice that were previously exposed to intact stable flies for 30 min exhibited significant analgesia when exposed 24-168 hr later to stable flies whose biting parts were removed, but not to nonbiting house flies. Administration of the specific N-methyl-D-aspartate (NMDA) antagonist NPC 12626 to fly-naive mice before exposure to intact flies, although not significantly reducing the analgesic response, blocked the subsequent conditioned analgesia. Naloxone, which blocked the intact biting fly-induced analgesia, did not alter the acquisition of the conditioned analgesic response to the altered stable flies. This demonstrates an NMDA-mediated acquisition of conditioned analgesia to a natural aversive stimulus.

Sex differences in opioid and N-methyl- d-aspartate mediated non-opioid biting fly exposure induced analgesia in deer mice

There is evidence for sex differences in responses to noxious stimuli and in the expression and mediation of analgesia. In particular, results of investigations with swim stress and the more ethologically appropriate stress of predator odor exposure have suggested sex differences in N-methyl- d-aspartate (NMDA) receptor system involvement in the mediation of analgesia. Whether or not this sex difference generalizes to other environmental stressors is, however, not clear. Biting flies are a natural aversive stimuli commonly encountered by wild and domestic animals and humans. The present study examined the opioid and non-opioid mediated nociceptive (50°C hot plate) responses of reproductive male and female deer mice, Peromyscus maniculatus, exposed to biting fly attack. A 30 min exposure to biting flies (stable flies, Stomoxys calcitrans (L.)) elicited a naloxone sensitive, opioid-mediated analgesia that was of a greater magnitude in males than in female deer mice. In contrast, a 5 min exposure to biting flies elicited a `on-opioid' analgesia that was of similar magnitude in both sexes and insensitive to both naloxone and the specific kappa opiate antagonist, nor-binaltorphimine. In male mice this non-opioid analgesia was antagonised by the competitive NMDA antagonist, NPC 1262, while in reproductive females the biting fly-induced analgesia was insensitive to NPC 12626. These results show that there are sex differences in NMDA involvement in the mediation of the non-opioid analgesia arising from brief exposure to the stress of biting fly attack. These data from a common, natural environmental challenge support the presence of basic sex difference in NMDA involvement in the mediation of stress-induced analgesia.

Synergism Between Stress Responses Induced by Biting Flies and Predator Odours

AbstractWe have previously shown that endogenous opioid systems (i.e. endorphins, enkephalins) are involved in the mediation of the behavioural and physiological effects of biting‐fly exposure. Opioid mediated reductions in pain sensitivity, or, more appropriately, nociceptive sensitivity (latency of a foot‐lifting response to a 50°C thermal surface), are evident in laboratory mice, Mus musculus domesticus, exposed to biting flies. Similar opioid‐mediated reductions in pain sensitivity (opioid analgesia) are also seen after exposure to a variety of other natural stressors such as the threat of predation. Here, we demonstrate that brief (30‐min) exposure of male mice to stable flies, Stomoxys calcitrans, significantly and synergistically augments either the concurrent or subsequent (60 min after fly exposure) analgesic effects induced by exposure to a predator (cat odour). These results demonstrate that the analgesic, and probably other opioid mediated behavioural and physiological stress responses induced by exposure to a relatively low number of biting flies, are markedly increased by the presence of another natural aversive stimulus. In addition, they show that biting‐fly exposure significantly exacerbates the effects of a subsequent stressful stimulus. These findings raise a possible mechanism whereby exposure to a low number of biting flies, which by themselves may not appear to have a great impact, can have marked behavioural and physiological consequences.

Sex differences in opioid and non-opioid mediated predator-induced analgesia in mice

The present study compared the nociceptive responses of male and female mice exposed to a predator, an ecologically relevant threatening stimulus. After 15 min of exposure to the presence of an experienced predatory cat, mice displayed a naloxone (1.0 mg/kg)-sensitive opioid mediated analgesic response, while after a brief 30-s exposure to the cat mice displayed a lower amplitude, relatively brief, non-opioid analgesia that was insensitive to naloxone and blocked by the serotonin-1A (5-HT 1A) agonist, 8-hydroxy-2-(di-n-propylamino)tetralin. Male mice displayed a significantly greater opioid mediated predator-induced analgesia than females, whereas female mice showed a significantly greater non-opioid, 5-HT 1A sensitive, analgesia than males. These results indicate that there are significant sex differences in both the opioid and non-opioid analgesic responses arising from exposure to a natural aversive stimulus.

Central 5-HT2 antagonists: A preclinical evaluation of a therapeutic potential.

A preclinical evaluation is presented of the serotonin 5-HT2 antagonists ritanserin and risperidone. Whereas ritanserin is a relative selective 5-HT2 antagonist, risperidone is a potent 5-HT2 and catecholamine antagonist. The pharmacological differences between both drugs are also observed in the drug discrimination test procedure. Using DOM, d-amphetamine and cocaine. Ritanserin was found active in animal models of anxiety using natural aversive stimuli; and in animal models of depression. Clear differences were observed between ritanserin and the benzodiazepines and between ritanserin and the tricyclic antidepressants. Risperidone was active in animal models of psychosis. Risperidone has, as opposed to classical neuroleptics such as haloperidol, less risks of inducing a dopamine D2 overblockade. Clinically, ritanserin is described as a thymostenic agent. Risperidone is an antipsychotic with therapeutic effects on both the positive and negative symptoms of schizophrenia and with a reduced risk of extrapyramidal side-effects.

Exposure to mosquitoes, Aedes togoi (Theo.), induces and augments opioid-mediated analgesia in mice

Mosquitoes and other biting flies are natural aversive stimuli commonly encountered by wild and domestic animals and by humans. We observed that male mice exposed for 30 min to a low density of female mosquitoes ( Aedes togoi) displayed significant increases in nociceptive responses which were indicative of the induction of analgesia. This analgesia was blocked by the prototypic opiate antagonist naloxone (1.0 mg/kg). Exposure to a novel stimulus had no significant effect on nociception, whereas 30 min of restraint stress induced a naloxone-reversible analgesia qualitatively similar to that observed after exposure to mosquitoes. Confinement in a small chamber for 30 min also had a significant analgesic effect whose amplitude and duration were markedly potentiated by concurrent exposure to mosquitoes. These results show that exposure to mosquitoes, and likely other biting flies, both induces an opioid-mediated analgesia and augments the analgesic effects of other stressful stimuli.

Psychopharmacology of ritanserin: Comparison with chlordiazepoxide

AbstractRitanserin, a central serotonin 5‐HT2 antagonist with complete LSD‐antagonist properties, was compared with the benzodiazepine chlordiazepoxide (CDZ) in different animal models of anxiety. In conflict procedures using electric shock as an inhibitory stimulus, a dose‐related disinhibition was observed with CDZ but not with ritanserin. In various other anxiety tests involving more natural aversive stimuli, ritanserin disinhibited exploratory behavior over a broad dose range while CDZ was marginally active. Clear differences between ritanserin and CDZ were also seen in drug discrimination test procedures. CDZ but not ritanserin had intrinsic discriminative stimulus properties. Furthermore, ritanserin did not generalize with CDZ or with fentanyl, LSD, cocaine, d‐amphetamine, or 8‐OHDPAT. These results suggest that ritanserin is unlikely to possess abuse potential. Unlike the benzodiazepine, ritanserin did not induce motor incoordination or sedation, was devoid of interaction with alcohol, and produced no state dependency. These experimental studies indicate that ritanserin possesses disinhibitory effects on exploratory behavior with a profile of activity diferent from that of benzodiazepines. Ritanserin thus has anxiety‐ and stress‐reducing effects in animal models of anxiety and the drug appears to be an original psychopharmacological compound, clinically characterized as a thymosthenic agent.

Leg position learning by an insect. I. A heat avoidance learning paradigm.

A new learning paradigm which employs a natural aversive stimulus, tightly constrains learned behavior and demonstrates learning in individual animals is described. Locusts were restrained so that only the femoro-tibial joint of a single metathoracic leg was free to move. Animals were required to maintain a particular range of femoro-tibial joint angle to avoid heating of the head. The position of the tibia was sampled by an on-line computer which set the limits of joint angle and controlled the aversive stimulus while storing data for further analysis. Control animals received patterns of aversive stimuli identical to those received by experimental animals but independent of their own joint position. Quantitative evaluation of the learned behavior of individual animals allowed the identification of three different behavioral strategies by which learning was achieved.

Locus of Control Orientation and Perception of "Hurricane" in Fifth Graders.

The effects of a natural aversive stimulus (Hurricane Eloise in 1975) on locus of control and perception of the concept "hurricane" were investigated among 463 fifth graders from Title I schools in two coastal cities along Florida's Panhandle. Although both cities were threatened, only one was hit. Of the 269 Ss in the city hit, 184 had fourth grade locus of control scores. The hypotheses were (a) children in the city hit would not show the expected age-related increase in internality; (b) children in the city hit would be more external than children in the city not hit; and (c) children in the city hit would perceive the concept "hurricane" more positively than children in the city not hit, largely because of the effect of the positive view of internals in the city hit. The third hypothesis was supported. The results were interpreted from perceptual defense and aversive conditioning viewpoints. The lack of support for the first two hypotheses is consistent with recent disaster literature on the lack of negative reaction of populations in the aftermath of natural disasters.