Genetic predisposition and the development of posttraumatic stress disorder in an animal model

King, Jean A.; Abend, Susan; Edwards, Emmeline

doi:10.1016/s0006-3223(01)01071-x

Cited by 60 publications

(31 citation statements)

References 40 publications

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“…Interestingly, in the non-handled rats, particularly the females, corticosterone levels were even lower than basal, indicating a hyporesponsive HPA axis. A blunted post-stress corticosterone response has also been found in an animal model of posttraumatic stress disorder [45], in rats neonatally treated with dexamethasone [46], and in rhesus monkeys exhibiting self-injurious behavior [47]. It thus appears that non-handled animals have a dysfunctional HPA axis.…”

Section: Discussionmentioning

confidence: 96%

Effect of Neonatal Handling and Sex on Basal and Chronic Stress-Induced Corticosterone and Leptin Secretion

et al. 2004

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Neonatal handling is an experimental paradigm for early experiences. It affects the programming of hypothalamo-pituitary-adrenal (HPA) axis function, known to be sexually dimorphic. Recently leptin, a hormone related to energy balance and secreted mainly by adipocytes, has been implicated in the stress response. We thus determined the effect of neonatal handling on plasma concentrations of corticosterone and leptin of male and female rats under basal conditions and after two consecutive chronic stressors: chronic forced swimming stress and chronic restraint. Handling resulted in lower basal corticosterone levels in both males and females and in a more efficient HPA response, with a large corticosterone surge following the first chronic stressor and a return to basal levels following the second. Handling also resulted in decreased plasma leptin concentrations in males, thus abolishing the sex difference in leptin levels. Furthermore, handling increased body weight while it decreased food intake under basal conditions. Food intake and body weight gain during chronic forced swimming was lower in handled than in non-handled males, while in females these parameters were not influenced by handling. In both males and females, handling resulted in decreased food intake and increased body weight loss during chronic restraint stress. Body weight loss during chronic restraint stress, which is considered an index of maladaptation and ‘depression’, was particularly pronounced in the handled females. Our results also showed that non-handled females had higher corticosterone and lower leptin levels than males under basal conditions and following each of the two chronic stressors. The present work suggests that early experiences, such as the mother–infant relationship, interact with endogenous factors, such as gonadal hormones, to determine the organism’s response to stressful stimuli during adulthood.

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Section: Discussionmentioning

confidence: 96%

Effect of Neonatal Handling and Sex on Basal and Chronic Stress-Induced Corticosterone and Leptin Secretion

et al. 2004

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“…The model has also been conducted using many different experimental procedures, depending on the study, which makes comparisons between studies difficult (Malberg and Duman 2003;Sherman et al 1979;Takase et al 2005;Wu et al 1999). Finally, the learned helplessness model is not only used to study depression, but has also been used to study post-traumatic stress disorder (Kikuchi et al 2008;King et al 2001) and has been implicated as a more relevant model for contextual fear (Amat et al 2008;Christianson et al 2008). Therefore, in rats, the model is not specific only for the study of depression and results may implicate factors associated with more than one psychological disorder.…”

Section: Discussionmentioning

confidence: 99%

Treatment with escitalopram but not desipramine decreases escape latency times in a learned helplessness model using juvenile rats

et al. 2009

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The learned helplessness model with PND 21 rats predicts the efficacy of escitalopram and the lack of efficacy of desipramine seen in the treatment of pediatric depression. These findings suggest that the use of PND 21 rats in a modified learned helplessness procedure may be a valuable model of human pediatric depression that can predict pediatric antidepressant efficacy and be used to study antidepressant mechanisms involved in pediatric depression.

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“…This raises the question whether predictive validity of these animal models is limited to detecting their antidepressant-like effects or whether these models could also be suitable for detecting non-BDZ-like anxiolytic activity of antidepressant drugs. This subject has been previously discussed for the learned helplessness model of depression (Yehuda and Antelman 1993;Maier 2001), as this paradigm has been proposed as a model of PTSD (King et al 2001).…”

Section: Discussionmentioning

confidence: 99%

Do animal models of anxiety predict anxiolytic-like effects of antidepressants?

2002

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Chronically administered antidepressant drugs, particularly selective serotonin (5-HT) reuptake inhibitors (SSRIs), are clinically effective in the treatment of all anxiety disorders, while the clinical effectiveness of "traditional" anxiolytics, such as benzodiazepines (BDZs), is limited to generalised anxiety disorder or acute panic attacks. This implies that animal models of anxiety should be sensitive to SSRIs and other antidepressants in order to have predictive validity. We reviewed the literature on the effects of antidepressants in the so-called animal models of anxiety and found that only the isolation-induced calls in guinea-pig pups may reveal anxiolytic-like action of all antidepressant classes after acute administration. Some other models, such as marble-burying or conditioned-freezing behaviours, and isolation- or shock-induced ultrasonic vocalisation models, may detect anxiolytic-like activity of acutely administered antidepressants, although the sensitivity of these models is usually limited to SSRIs and other drugs affecting 5-HT uptake. The predictive validity of models of "anxiety", such as the plus-maze and light-dark transition tests or stress-induced hyperthermia, appears to be limited to BDZ-related drugs. Far less work has been done on chronic administration of antidepressants in animal anxiety models. Unless and until such studies have been undertaken, the true predictive value of the anxiety models will remain unknown.

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Genetic predisposition and the development of posttraumatic stress disorder in an animal model

Cited by 60 publications

References 40 publications

Effect of Neonatal Handling and Sex on Basal and Chronic Stress-Induced Corticosterone and Leptin Secretion

Effect of Neonatal Handling and Sex on Basal and Chronic Stress-Induced Corticosterone and Leptin Secretion

Treatment with escitalopram but not desipramine decreases escape latency times in a learned helplessness model using juvenile rats

Do animal models of anxiety predict anxiolytic-like effects of antidepressants?

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