Expression Of Defensive Behaviors Research Articles

The modulation of striatonigral and nigrotectal pathways by CB1 signalling in the substantia nigra pars reticulata regulates panic elicited in mice by urutu-cruzeiro lancehead pit vipers

Cannabinoid receptor type 1 (CB1R) is widely distributed in the substantia nigra pars reticulata (SNpr). However, the role of CB1R at the SNpr level in threatening situations is poorly understood. We investigated the role of CB1R in the SNpr on the expression of fear responses in mice confronted with urutu-cruzeiro pit vipers. First, a bidirectional neurotracer was injected into the SNpr; then, immunostaining of the vesicular GABA transporter was conducted at the levels of the striatum (CPu) and deep layers of the superior colliculus (dlSC). In addition, CB1R immunostaining and GABA labelling were performed in the SNpr. Using a prey-versus-snake paradigm, mice were pretreated with the CB1R antagonist AM251 (100 pmol) and treated with the endocannabinoid anandamide (AEA, 5 pmol) in the SNpr, followed by bicuculline (40 ng) in the dlSC, and were then confronted with a snake. Bidirectional neural tract tracers associated with immunofluorescence showed the GABAergic striatonigral disinhibitory and nigrotectal inhibitory pathways. Furthermore, we showed that CB1R labelling was restricted to axonal fibres surrounding SNpr GABAergic cells. We also demonstrated a decrease in the defensive behaviours of mice treated with AEA in the SNpr, but this effect was blocked by pre-treatment with AM251 in this structure. Taken together, our results show that the panicolytic consequences of the AEA enhancement in the SNpr are signalled by CB1R, suggesting that CB1R localised in axon terminals of CPu GABAergic neurons in the SNpr modulates the activity of the nigrotectal GABAergic pathway during the expression of defensive behaviours in threatening situations.

Panicolytic-like effect of µ1-opioid receptor blockade in the inferior colliculus of prey threatened by Crotalus durissus terrificus pit vipers

The endogenous opioid peptide system has been implicated in the neural modulation of fear and anxiety organised by the dorsal midbrain. Furthermore, previous results indicate a fundamental role played by inferior colliculus (IC) opioid mechanisms during the expression of defensive behaviours, but the involvement of the IC µ1-opioid receptor in the modulation of anxiety- and panic attack-related behaviours remains unclear. Using a prey-versus-snake confrontation paradigm, we sought to investigate the effects of µ1-opioid receptor blockade in the IC on the defensive behaviour displayed by rats in a dangerous situation. Specific pathogen-free Wistar rats were treated with microinjection of the selective µ1-opioid receptor antagonist naloxonazine into the IC at different concentrations (1.0, 3.0 and 5.0 µg/0.2 µL) and then confronted with rattlesnakes ( Crotalus durissus terrificus). The defensive behavioural repertoire, such as defensive attention, flat back approach (FBA), startle, defensive immobility, escape or active avoidance, displayed by rats either during the confrontations with wild snakes or during re-exposure to the experimental context without the predator was analysed. The blockade of µ1-opioid receptors in the IC decreased the expression of both anxiety-related behaviours (defensive attention, FBA) and panic attack-related responses (startle, defensive immobility and escape) during the confrontation with rattlesnakes. A significant decrease in defensive attention was also recorded during re-exposure of the prey to the experimental apparatus context without the predator. Taken together, these results suggest that a decrease in µ1-opioid receptor signalling activity within the IC modulates anxiety- and panic attack-related behaviours in dangerous environments.

Pain chronification and chronic pain impair a defensive behavior, but not the ability of acute pain to facilitate it, through the activation of an endogenous analgesia circuit.

The endogenous ability to decrease pain perception during life-threatening situations is crucial to the prevention of recuperative behaviors and to leave the subject free to engage in appropriated defensive responses. We have previously shown that acute pain activates the ascending nociceptive control-an endogenous analgesia circuit dependent on opioid mechanisms within nucleus accumbens-to facilitate the tonic immobility response, an innate defensive behavior. Now we asked whether chronic pain and pain chronification impairs either the tonic immobility response or the ability of acute pain to facilitate it by activating the ascending nociceptive control. We found a significant decrease in the duration of the tonic immobility response in rats during the induction and maintenance phases of the persistent mechanical hyperalgesia. This finding suggests that chronic pain and its development impair defensive responses. However, during the induction and maintenance phases of persistent hyperalgesia, the ascending nociceptive control activation, by a forepaw capsaicin injection, increased the tonic immobility response, an effect prevented by the blockade of μ-opioid receptors within nucleus accumbens. This finding suggests that pain chronification and chronic pain do not prevent the ability of acute pain to facilitate the defensive behavior of tonic immobility by activating the ascending nociceptive control. Therefore, although chronic pain states decrease the ability to engage in a defensive behavior, they may not prevent the expression of defensive behaviors during life-threatening situations accompanied by acute pain. The biological purpose of such a mechanism may be to increase the chances of survival of a wounded subject exposed to acute pain in a novel life-threatening situation. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Brief optogenetic inhibition of rat lateral or ventrolateral periaqueductal gray augments the acquisition of Pavlovian fear conditioning.

The midbrain periaqueductal gray (PAG) coordinates the expression and topography of defensive behaviors to threat and also plays an important role in Pavlovian fear learning itself. Whereas the role of PAG in the expression of defensive behavior is well understood, the relationship between the activity of PAG neurons and fear learning, the exact timing of PAG contributions to learning during the conditioning trial, and the contributions of different PAG columns to fear learning are poorly understood. We assessed the effects of optogenetic inhibition of lateral (LPAG) and ventrolateral PAG (VLPAG) neurons on fear learning. Using adenoassociated viral vectors expressing halorhodopsin, we show that brief optogenetic inhibition of LPAG or VLPAG during delivery of the shock unconditioned stimulus (US) augments acquisition of contextual or cued fear conditioning, and we also show that this inhibition augments postencounter defensive responses to a nonnoxious threat. Taken together, these results show that LPAG and VLPAG serve a key role in the regulation of Pavlovian fear learning at the time of US delivery. These findings provide strong support for existing models that state that LPAG and VLPAG contribute to a fear prediction error signal determining variations in the effectiveness of the aversive US in supporting learning. (PsycINFO Database Record

English

Agave sisalana is a plant belonging to the Agavaceae family. Sisal juice is constituted of steroidic saponins which are precursor molecules of many pharmacologically active steroids. These precursor molecules can act in brain structures that are related to the modulation of emotional disorders. They can act on energy metabolism or directly on the absorptive process of fats. The objective of this research was to identify the biocompounds present in A. sisalana juice, and to evaluate the effect of different extracts on the expression of defensive behaviours of rats in elevated plus maze and open field tests, and body weight, in a condition that corresponds to an induced menopause. Wistar rats were subjected to bilateral ovariectomy or to a sham surgical procedure under anaesthesia. Following surgery, they were treated gavage with sisal juice - concentrated crude juice (CCJ): 500 or 1000 mg/kg; dried extract (DE): 50, 100 or 200 mg/kg; dry mucilage extract (DME): 25, 50 or 100 mg/kg; and intermediate product (IP): 25, 50 or 100 mg/kg; or distilled water. The results showed the presence of coumarins, flavonoids, condensed tannins, free anthraquinones, alkaloids and saponins in the sisal juice. Both CCJ and DE (100 mg/kg) caused weight loss without alteration of defensive behaviours related to the manifestation of anxiety. As saponins were identified in DE in significant amounts, the observed effects were attributed to this component. Such findings point to A. sisalana as a plant that could potentially be used to treat weight gain during menopause. Key words: Agave sisalana, steroidic saponins, body weight, anxiety, plus-maze, females, ovariectomy.

Medial prefrontal cortex Transient Receptor Potential Vanilloid Type 1 (TRPV1) in the expression of contextual fear conditioning in Wistar rats

Contextual fear is evoked by re-exposing an animal to an environment that has been previously paired with an aversive or unpleasant stimulus. It can be assessed by freezing and cardiovascular changes such as increase in mean arterial pressure and heart rate. A marked increase in neuronal activity is associated with contextual fear conditioning, especially in limbic structures involved with defense reactions, such as the ventral portion of medial prefrontal cortex. Given the fact that transient receptor potential vanilloid type 1 (TRPV1) receptors could be involved in the expression of defensive behavior, the present work tested the hypothesis that TRPV1 manipulation in the ventromedial prefrontal cortex (vMPFC) modulates the expression of contextual conditioned fear. Male Wistar rats received bilateral microinjections into the vMPFC of the TRPV1 receptor antagonists capsazepine (1, 10, and 60nmol/200nL) or 6-iodonordihydrocapsaicin (3nmol/200nL), and the TRPV1 agonist capsaicin (1nmol/200nL) preceded by vehicle or 6-iodonordihydrocapsaicin before re-exposure to the experimental chamber for 10min, 48h after conditioning in two different protocols distinct by their aversiveness. Both antagonists reduced the freezing and cardiovascular responses in the high aversive protocol. Capsaicin caused an increase in fear-associated responses that could be blocked by 6-iodonordihydrocapsaicin. Our results indicate that TRPV1 receptors located in the vMPFC have a tonic involvement in the modulation of the expression of contextual fear conditioning.

Serotonergic neural links from the dorsal raphe nucleus modulate defensive behaviours organised by the dorsomedial hypothalamus and the elaboration of fear-induced antinociception via locus coeruleus pathways

Decrease of γ-aminobutyric acid (GABA)-mediated neurotransmission in the dorsomedial hypothalamus (DMH) evokes instinctive fear-like responses. The aim of the present study was to investigate the involvement of the serotonin (5-HT)- and norepinephrine-mediated pathways of the endogenous pain inhibitory system, including the dorsal raphe nucleus (DRN) and the locus coeruleus (LC), in the defensive responses and antinociceptive processes triggered by the blockade of GABAergic receptors in the DMH. The intra-hypothalamic microinjection of the GABAA receptor antagonist bicuculline (40 ng/200 nL) elicited elaborate defensive behaviours interspersed with exploratory responses. This escape behaviour was followed by significantly increased pain thresholds, a phenomenon known as fear-induced antinociception. Furthermore, at 5 and 14 days after DRN serotonin-containing neurons were damaged using the selective neurotoxin 5,7-dihydroxytryptamine (5,7-DHT), the frequency and duration of alertness and escape behaviour evoked by the GABAA receptor blockade in the DMH decreased, as well as fear-induced antinociception. Pre-treatment with the non-selective 5-HT receptor antagonist methysergide, the 5-HT2A/2C receptor antagonist ketanserin and the 5-HT2A receptor selective antagonist R-96544 in the LC also decreased fear-induced antinociception, without significant changes in the expression of defensive behaviours. These data suggest that the serotonergic neurons of the DRN are directly involved in the organisation of defensive responses as well as in the elaboration of the innate fear-induced antinociception. However, serotonin-mediated inputs from the NDR to the LC modulate only fear-induced antinociception and not the defensive behaviours evoked by GABAA receptor blockade in the DMH.

5-HT2 receptor mechanisms of the dorsal periaqueductal gray in the conditioned and unconditioned fear in rats

It is well known that 5-HT(2) mechanisms modulate the defensive behavior produced by the stimulation of the dorsal periaqueductal gray (dPAG). However, in spite of the notion that past stressful experiences play a role in certain types of anxiety, only studies with the stimulation of the dPAG of rats without previous aversive experience have been conducted so far. We investigated the mediation of 5-HT(2) receptors of the dPAG in rats previously submitted to contextual fear conditioning (CFC). Defensive behaviors induced by the activation of the dPAG were assessed by measuring the lowest intensity of electric current applied to this structure (threshold) able to produce freezing and escape responses during the testing sessions of CFC in which animals were placed in a context previously paired to footshocks. The 5-HT(2) function of the dPAG in this condition was evaluated by local injections of alpha-methyl-5-HT (20 nmol/0.2 mul) and ketanserin (5 and 10 nmol/0.2 mul), selective agonist and antagonist of 5-HT(2) receptors, respectively. In accordance with previous studies, alpha-methyl-5-HT increased the aversive thresholds (antiaversive effects) in naive rats, and injection of ketanserin into the dPAG did not produce significant effects. On the other hand, ketanserin decreased in a dose-dependent manner the freezing threshold (proaversive effect) determined by the dPAG electrical stimulation, whereas alpha-methyl-5-HT continued to show antiaversive effects in animals under CFC. The present results suggest that past stressful experience can produce changes in the synaptic function of 5-HT(2) receptors within the dPAG with important impact on the expression of defensive behaviors.

Behavioral, central monoaminergic and hypothalamo–pituitary–adrenal axis correlates of fear-conditioned analgesia in rats

Fear-conditioned analgesia is an important survival response which is expressed upon re-exposure to a context previously paired with a noxious stimulus. The aim of the present study was to characterize further the behavioral, monoaminergic and hypothalamo–pituitary–adrenal axis alterations associated with expression of fear-conditioned analgesia. Rats which had received footshock conditioning 24 h earlier, exhibited reduced formalin-evoked nociceptive behavior upon re-exposure to the footshock chamber, compared with non-footshocked formalin-treated rats. Intra-plantar injection of formalin reduced the duration of contextually-induced freezing and 20–40 kHz ultrasound emission. Intra-plantar injection of formalin to non-footshocked, non-conditioned rats did not induce ultrasonic vocalizations. Intra-plantar injection of formalin to footshock-conditioned rats, significantly increased tissue levels of 3,4-dihydroxyphenylacetic acid and the 3,4-dihydroxyphenylacetic acid:dopamine ratio in the periaqueductal gray and reduced levels of dopamine in the thalamus, compared with saline-treated footshocked controls. Non-footshocked, non-conditioned rats were capable of mounting a robust formalin-evoked increase in plasma corticosterone levels. Moreover, plasma corticosterone levels were significantly higher in saline-treated, footshock conditioned rats compared with saline-treated non-footshocked rats and levels did not differ between saline- and formalin-treated footshock conditioned rats. Assessment of the effects of the intra-plantar injection procedure revealed an attenuation of short-term extinction of contextually-induced freezing in rats anesthetized for intra-plantar injection of saline compared with non-anesthetized, non-injected rats as well as discrete effects on monoamines, their metabolites and plasma corticosterone levels. These data extend behavioral characterization of the phenomenon of fear-conditioned analgesia and suggest that measurement of ultrasound emission may be used as an ethologically relevant index of the defense response during fear-conditioned analgesia. Ultrasonic vocalization may also be a useful behavioral output to aid separation of nociception and aversion. The data provide evidence for discrete alterations in dopaminergic activity in the periaqueductal gray and thalamus and for altered hypothalamo–pituitary–adrenal axis activity following expression of defensive behavior.

Defensive behavior and hippocampal cell proliferation: Differential modulation by naltrexone during stress.

The present study investigated the role of endogenous opioids in the expression of defensive behaviors (DBs) and the suppression of cell proliferation (CP) in the dentate gyrus (DG) induced by exposure to predator odor, trimethyl thiazoline (TMT). Adult male rats were injected with either naltrexone (an opioid antagonist, 5 mg/kg) or saline 30 min before exposure to either TMT or a control odor. Behavior was scored for the first 15 min of odor exposure. Bromodeoxyuridine (BrdU, 200 mg/kg) was then injected, and the rats were perfused 1 hr later. Exposure to TMT increased the expression of DBs and suppressed the number of proliferating cells in the DG. Pretreatment with naltrexone attenuated the effects of TMT on DB expression but did not attenuate the effects of TMT on CP. In addition, naltrexone administration suppressed CP in the absence of TMT. These results demonstrate a dissociation between DBs and regulation of CP in the DG.

Septal lesions potentiate freezing behavior to contextual but not to phasic conditioned stimuli in rats.

The effects on freezing behavior elicited by contextual and phasic conditioned stimuli (CSs) were examined in rats with septal lesions. Two weeks after surgery, blocks of 2 conditioning trials consisting of a tone (10 kHz, 75 dB, 20 s) paired with a footshock (500 ms, 0.5 mA) were presented on 2 consecutive days. Tone-alone trials were presented each day thereafter until extinction criterion was met. Septal lesions were found to potentiate the freezing response elicited by contextual stimuli but had no effect on freezing elicited by the phasic CS. The septum thus appears to be involved in the acquisition and/or expression of defensive behaviors elicited by contextual stimuli.

Prey Specificity in Chrysopa: An Interspecific Comparison of Larval Feeding and Defensive Behavior

To examine pathways in the evolution of prey specialization in insects, we conducted a comparative experimental analysis of larval behavior in two sympatric predacious sister—species (Chrysopa quadripunctata, a generalist, and C. slossonae, a specialist on the woolly alder aphid). Responses of the larvae to food (Myzus persicae) and camouflaging material (waxy secretions from woolly alder aphids or exuviae from M. persicae) were quantified during four discrete developmental periods. Our analysis revealed species specific, ontogenetic, and environmentally induced variation in larval defensive and feeding behavior. The pattern of interspecific variation indicates that larval behavior could have subserved two processes in the evolution of prey specialization in the sister—species' progenitor: establishment on a specific prey and adaptation to the prey. First, the presence of the woolly alder aphid's secretions results in generalist larvae camouflaging themselves to a degree that rivals that of the specialist. Such phenotypic plasticity could have promoted the progenitor's initial adoption of the ant—tended woolly alder aphid as prey and its wool as a source of camouflaging material. Second, quantitative differences between the generalist's and specialist's behavior indicate that adaptation to the woolly alder aphid did not require the acquisition of novel behavioral traits in the larvae. It involved modifications in the expression of defensive behavior that existed in the generalist ancestor and alterations in the ability to attack and feed on robust prey.

Defensive Behaviors in Infant Rhesus Monkeys: Ontogeny and Context-dependent Selective Expression

We examined the ontogeny of the infant rhesus monkey's defensive behaviors and the ability to modulate them in response to specific environmental cues. Rhesus infants in 4 age groups (N = 8 per group) were briefly separated from their mothers and tested under 3 conditions: alone, in the presence of a human who averted his gaze, and in the presence of a human staring at them. Infants as young as 0 to 2 weeks displayed defensive behaviors but did not selectively respond to the human's presence or direction of gaze. By 9 to 12 weeks of age, infants modulated their responses in relation to the parameters of the threat. At this age, infant rhesus monkeys undergo cognitive and emotional changes associated with brain development similar to those in human infants 7 to 12 months old. This also is the time when human infants engage in complex emotional and behavioral responses to threatening situations. Understanding the development and expression of defensive behaviors in infant monkeys should be applicable to similar issues in emotional development of human infants.