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Article
Aptations or pathologies? Long-term changes in brain and behavior after a single exposure to severe threat.
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Year: 2004

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The experience of a single threatening situation may alter the behavior of an animal in a long-lasting way. Long-lasting changes in behavior have been induced in laboratory animals to model and investigate the development and neural substrate of human psychopathologies. Under natural conditions, however, changes in behavior after an aversive experience may be adaptive because behavioral modifications allow animals to adjust to a threat for extended periods of time. In the laboratory setting, properties of the aversive situation and the potential of the animal to respond to the threat may be altered and lead to extensive, prolonged changes, indicating a failure in behavioral regulation. Such long-term changes seem to be mediated by neuronal alterations in components of the fear pathway. To understand psychopathologies, determinants of exaggerated responsivity and the underlying molecular and neural processes have to be analyzed in a comparative way under conditions that produce normal and abnormal fear and anxiety. (C) 2003 Elsevier Ltd. All rights reserved


Article
Ontogeny of defensive behavior and analgesia in rat pups exposed to an adult male rat.
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Year: 1998

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Aversive situations may reduce nociception. The mechanism underlying such analgesia has been suggested to involve the interaction between the two separate but interconnected motivational systems ''defense'' and ''pain.'' To determine the developmental course of defense and nociception, these processes were analyzed during early ontogeny in rats. To elicit a defensive reaction, a huddle of preweanling rat pups was exposed to an unfamiliar, unrelated adult male, or, for comparison, to the mother. On postnatal Day 7 the pups did not show a behavioral reaction to the presence of the mother or the male, and no reduction in nociceptive threshold in a thermal paw withdrawal test. On Day 14, pups in the presence of the male stopped ongoing behaviors and became immobile, and showed reduced paw withdrawal after the exposure. At Day 21, 22 pups of 32 became immobile when exposed to the male, whereas 10 pups explored the partition separating them from the male. Neither group showed reduced paw withdrawal. Immobility was considered a defensive reaction because it reduces auditory and visual cues and therefore the probability of being detected. The developmental course of immobility seems to reflect both the changes in threat imposed on the pups by a potentially infanticidal male and the ability of pups to react to that threat. The reduction in paw withdrawal that followed male exposure indicates an inhibitory mechanism. It is discussed whether the activation of the defense system results in an inhibition of nociception. (C) 1998 Elsevier Science Inc


Article
mu opioid receptors in the ventrolateral periaqueductal gray mediate stress-induced analgesia but not immobility in rat pups.
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Year: 2000

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Rat pups become immobile and analgesic when exposed to an adult male rat. The aim of this study was to determine whether these reactions are under the control of endogenous opioids and to determine the role of the midbrain periaqueductal gray (PAG), which mediates stress-induced immobility and analgesia in adult animals. In Experiment 1, 14-day-old rats were injected systemically with the general opioid receptor antagonist naltrexone (1 mg/kg), which blocked male-induced analgesia to thermal stimulation but did not affect immobility. In Experiment 2, the selective mu opioid receptor antagonist D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP; 50 or 100 ng/200 nl) was microinjected into the ventrolateral and lateral PAG. CTOP suppressed male-induced analgesia when injected into the ventrolateral PAG. Male-induced immobility was not affected by CTOP. Male proximity therefore seems to induce analgesia in rat pups by releasing endogenous opioids that bind to mu opioid receptors in the ventrolateral PAG


Article
Developmental changes in responsivity to threat are stimulus-specific in rats.
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Year: 2001

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During early ontogeny, stimuli that pose a threat to an animal change. Unrelated adult male rats may kill young rats, bur infanticide ends around weaning. Predation, on the other hand may increase during early ontogeny when mts begin to extend their activity range. We investigated the developmental course of two defensive responses, immobility and analgesia, in young rats exposed to an adult male rat or to predator cues. Preweaning 14-day-old mts became immobile and analgesic when exposed to the male and showed immobility but not analgesia when exposed to cat odor On Day 26, around weaning, the presence of the male rat no longer induced immobility and analgesia whereas cat odor produced higher levels of immobility and analgesia compared to control and male-exposed animals. This developmental change in responsivity may reflect the differences in the risk of being harmed by a male or a cat during different periods of ontogeny. (C) 2001 John Wiley & Sons, Inc


Article
The effect of periaqueductal gray lesions on responses to age-specific threats in infant rats.
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Year: 2000

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During early ontogeny infant rats show specific responses to a variety of age-dependent threatening situations. When isolated from nest and dam, they emit ultrasonic vocalizations and show decreased reactivity to noxious stimulation, or analgesia. When exposed to an unfamiliar adult male, they become immobile and analgesic. The midbrain periaqueductal gray (PAG) is an important area within the circuitry that controls responses to threatening stimuli in the adult. Little is known about the functions of the PAG in early life. It was hypothesized that the PAG mediates the responses to the age-specific threats social isolation and male exposure in the infant rat. Rat pups were lesioned electrolytically either in the lateral or the ventrolateral PAG on postnatal day 7, tested in social isolation on day 10, and exposed to a male on day 14. On day 10 during isolation, ultrasonic vocalizations and isolation-induced analgesia were decreased in both lesion groups. On day 14, male-induced immobility and analgesia were decreased in ventrally lesioned animals. In conclusion, the PAG seems to play a developmentally continuous role in age-specific responses to threat such as ultrasonic vocalization, analgesia, and immobility. (C) 2000 Elsevier Science B.V. All rights reserved


Article
Rat pups reduce ultrasonic vocalization after exposure to an adult male rat.
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Year: 2003

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We examined how the experience of a threatening stimulus alters subsequent behavior in a situation where the immediate threat is absent. A small huddle of 12-day-old rats was exposed to a potentially infanticidal adult male rat for 5 min. During male exposure, pups were significantly more immobile than control pups. Thirty, 60, and 180 min after male exposure, the pups were isolated for 5 min from litter and dam in an unfamiliar environment. When isolated, pups that had been previously exposed to the male emitted significantly fewer ultrasonic vocalizations than controls, but did not differ in immobility. Low levels of vocalization were apparent 30 and 60 min after male exposure and were not evident at 180 min. The pups seemed to have adjusted their behavior to a potential male threat in a different context for a limited period of time. (C) 2003 Wiley Periodicals, Inc


Article
Mother lowers glucocorticoid levels of preweaning rats after acute threat.

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Exposure to a deadly threat, an adult male rat, induced the release of corticosterone in 14-day-old rat pups. The endocrine stress response was decreased when the pups were reunited with their mother immediately after exposure. These findings demonstrate that social variables can reduce the consequences of an aversive experience


Article
Age-specific threats induce CRF expression in the paraventricular nucleus of the hypothalamus and hippocampus of young rats.

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Young animals respond to threatening stimuli in an age-specific way. Their endocrine and behavioral responses reflect the potential threat of the situation at a given age. The aim of the present study was to determine whether corticotropin-releasing factor (CRF) is involved in the endocrine and behavioral responses to threat and their developmental changes in young rats. Preweaning 14-day-old and postweaning 26-day-old rats were exposed to two age-specific threats, cat odor and an adult male rat. The acute behavioral response was determined during exposure. After exposure, the time courses of the corticosterone response and of CRF expression in the paraventricular nucleus of the hypothalamus (PVN) and in extrahypothalamic areas were assessed. Preweaning rats became immobile when exposed to cat odor or the male rat, whereas postweaning rats became immobile to cat odor only. Male exposure increased serum corticosterone levels in 14-day-old rats, but cat odor failed to increase levels at either age. Exposure induced elevation of CRF mRNA levels in the PVN that paralleled changes in corticosterone levels. CRF may thus play a role in endocrine regulation and its developmental changes during early life. Neither cat odor nor the adult male altered CRF mRNA levels in the bed nucleus of the stria terminalis (BNST) or the amygdala, but both stimuli increased levels in the hippocampus. Hippocampal CRF mRNA expression levels did not parallel cat odor or male-induced immobility, indicating that CRF is not involved in this response in young rats but may be involved in aspects of learning and memory. (C) 2004 Elsevier Inc. All rights reserved


Article
Olfactory based spatial learning in neonatal mice and its dependence on CaMKII.
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Year: 2000

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Spatial learning and memory involves the ability to encode geometric relationships between perceived cues and depends critically on the hippocampus. Visually guided spatial learning has been demonstrated in adult animals. As infant animals rely heavily on olfaction, olfactory based spatial learning was assessed in infant mice. When 12-day-old pups were displaced from their nest, they learned within a few training trials to use the spatial pattern of odor cues to move back to the nest. However, mouse pups that over-expressed Ca2+/calmodulin-dependent protein kinase (CaMKII) in hippocampal neurons were impaired in olfactory based spatial learning. NeuroReport 11:1051-1055 (C) 2000 Lippincott Williams & Wilkins


Article
Stress-induced preproenkephalin mRNA expression in the amygdala changes during early ontogeny in the rat.

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Stress activates endogenous opioids that modulate nociceptive transmission. Exposure to a potentially infanticidal adult male rat suppresses pain-related behaviors in pre-weaning but not in older rats. This male-induced analgesia is mediated by I opioid receptors in the periaqueductal gray, a midbrain structure that is innervated by amygdala projections. To determine whether enkephalin, a l and d opioid receptor agonist, is activated by male exposure, mRNA levels of its precursor, preproenkephalin, were measured in subdivisions of the amygdala and the periaqueductal gray. In 14-day-old but not in 21-day-old rats, 5 min of male exposure induced analgesia to heat and increased preproenkephalin mRNA levels in the central nucleus of the amygdala but not in the periaqueductal gray. The change in the activation of enkephalinergic neurons in the central amygdala may contribute to the change in stress-induced analgesia during early ontogeny. (C) 2002 IBRO. Published by Elsevier Science Ltd. All rights reserved

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