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A Practical Approach, Second Edition=Ronald D. Ho.pdf

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POSTNATAL DEVELOPMENTAL MILESTONES 1123Puppies that had only social contact to other dogs during the critical periods of socialization (i.e.,5-7 weeks of age) exhibited extreme fear when introduced to human contact (Freedman et al., 1961).Non-Human PrimatesAround 2.5-3 months of age, but not before, monkeys separated from their mothers become agitated,emit frequent distress vocalizations, and show a distinct increase in adrenocorticotropic hormoneresponse (Harlow, 1959). Rhesus infants also begin to demonstrate fear reactions to threateningpictures, strange objects, and novel situations around this age. If a human enters a room with cagedmonkeys, the animals become silent and freeze, which are both signs of fear to unfamiliarity.Rhesus infants raised with an inanimate object do not show signs of fear to a novel location untilthey are 3-4 months old (Harlow, 1959).Much work has been done to investigate the CNS systems involved in development of fear. Thefreezing response appears to be influenced by gamma-aminobutyric acid systems (Herschkowitz et al.,1997), while the distress cries are influenced by opiate systems. Both the anterior cingulated cortexand the amygdala, which have high densities of opiate receptors, participate in the production of distresscalls. Bilateral ablation of the amygdala at 2.5 months produced a significant decrease in fear reactionsto novel situations. Control animals who showed fear to an unfamiliar place took three times longerthan lesioned animals to leave a familiar cage and enter an unfamiliar one. Amygdalectomized monkeysalso showed significantly fewer fear reactions to pictures of monkey faces expressing fear.The amygdala has been implicated in the mediation of emotional and species-specific socialbehavior. The amygdala in adults is involved in determining whether an object or organism ispotentially dangerous. If danger is detected, it coordinates a variety of other brain regions to producea species-typical response to avoid the danger. Therefore, the amygdala contributes to learningwhat is dangerous in the environment. Selective amygdala lesions in 2-week old macaques resultedin less fear of novel objects (e.g., rubber snakes) when the animals were tested at 6-8 months ofage. <strong>Ho</strong>wever, the lesioned animals displayed substantially more fear behavior than controls duringsocial interactions. These results suggest that neonatal amygdala lesions dissociate a system thatmediates social fear from one that mediates fear of inanimate objects. Thus, amygdala lesions earlyin development have different effects on social behavior than lesions produced in adulthood, whichdecrease fear of inanimate objects and increase fear during social behavior (Prather et al., 2001).Conclusions for Fear Response DevelopmentEvaluations of the development of a fear response in juvenile toxicity studies may provide someinsight because it appears to develop postnatally in all common laboratory species. <strong>Ho</strong>wever,methods to evaluate the development of the fear response are not widely applicable to screeningtoxicity studies.Table 7Fear ResponseSummary of Fear ResponseHuman7–9 monthsRat PND 20–30Dog3–7 weeksNon-Human Primate 2.5–4 monthsApproximate Postnatal AgeAbility Begins to EmergesDevelopment of Sleep CyclesThe sleep-wake cycle is developed postnatally in many species and is thought to be critical in thedevelopment of cognitive abilities.© 2006 by Taylor & Francis Group, LLC

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