Psychobiologic Mechanisms of Posttraumatic Stress Disorder

Charney, Dennis S.

doi:10.1001/archpsyc.1993.01820160064008

Cited by 567 publications

(252 citation statements)

References 178 publications

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“…As one of the biological models of P TSD and depression predicts (cf. Post et al, 1981;Charney et al, 1993), such effects might be amplified by stress-induced kindling of various limbic areas, including the amygdala and BNST. The amygdala and BNST show particularly dense concentrations of CRH cell bodies and receptors (Cummings et al, 1983;De Souza et al, 1984;Sawchenko and Swanson, 1985;Sakanaka et al, 1987;Chalmers et al, 1995;Lovenberg et al, 1995), and chronic stress increased CRH mRNA in the CeA and BNST (Mamalaki et al, 1992;Makino et al, 1994aMakino et al, ,b, 1995.…”

Section: Discussionmentioning

confidence: 99%

Role of the Hippocampus, the Bed Nucleus of the Stria Terminalis, and the Amygdala in the Excitatory Effect of Corticotropin-Releasing Hormone on the Acoustic Startle Reflex

1997

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Previously, we demonstrated that transection of the fimbria/ fornix blocked the excitatory effect of corticotropin-releasing hormone (CRH) on startle (CRH-enhanced startle), suggesting that the hippocampus and its efferent target areas that communicate via the fimbria may be critically involved in CRHenhanced startle. The bed nucleus of the stria terminalis (BNST) receives direct projections from the ventral hippocampus via the fimbria/fornix. Therefore, the role of the ventral hippocampus, the BNST, and the amygdala in CRH-enhanced startle was investigated. NMDA lesions of the BNST completely blocked CRH-enhanced startle, whereas chemical lesions of the ventral hippocampus and the amygdala failed to block CRH-enhanced startle. However, the same amygdala-lesioned animals showed a complete blockade of fear-potentiated startle, a conditioned fear response sensitive to manipulations of the amygdala. In contrast, BNST-lesioned rats had normal fear-potentiated startle. This indicates a double dissociation between the BNST and the amygdala in two different paradigms that enhance startle amplitude. Microinfusions of CRH into the BNST, but not into the ventral hippocampus, mimicked intracerebroventricular CRH effects. Furthermore, infusion of a CRH antagonist into the BNST blocked CRH-enhanced startle in a dose-dependent manner. Control studies showed that this blockade did not result from either leakage of the antagonist into the ventricular system or a local anesthetic effect caused by infusion of the antagonist into the BNST. The present studies strongly suggest that CRH in the CSF can activate the BNST, which could lead to activation of brainstem and hypothalamic BNST target areas involved in anxiety and stress responses. Key words: bed nucleus of the stria terminalis (BNST ); amygdala; hippocampus; corticotropin-releasing hormone (CRH); startle; anxiety; fearIntracerebroventricular inf usion of corticotropin-releasing hormone (CRH) elicits a constellation of behavioral, physiological, and endocrinological changes similar to those produced by natural stressors (cf. Dunn and Berridge, 1990). Thus far, however, the exact anatomical sites responsible for these behavioral and physiological actions of CRH after intracerebroventricular administration have not been identified. As part of an effort to delineate the neural circuitry underlying intracerebroventricular CRH effects, recently we investigated a possible involvement of the septum, using increased acoustic startle amplitude after CRH (CRH-enhanced startle) as a behavioral measure (Lee and Davis, 1997). Electrolytic lesions of the whole septum and the medial septum, but not the lateral septum, blocked CRH-enhanced startle. However, fiber-sparing chemical lesions of the medial septum failed to block CRH-enhanced startle, suggesting that the blockade seen with electrolytic lesions was probably caused by damage to fibers of passage, presumably the fornix. Supporting this conclusion, f unctional lesions of the fornix induced by knife cuts of the fimbria /fornix complete...

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Section: Discussionmentioning

confidence: 99%

Role of the Hippocampus, the Bed Nucleus of the Stria Terminalis, and the Amygdala in the Excitatory Effect of Corticotropin-Releasing Hormone on the Acoustic Startle Reflex

1997

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“…It has been suggested that PTSD is a disorder caused in part by the failure of extinction of predictable post-traumatic physiological and psychological reactions. Thus, deficits in extinction of conditioned fear have been proposed as a basis for the sustained anxiety responses seen in PTSD and treatment-resistant phobias (Charney et al, 1993;Rothbaum and Davis, 2003).…”

Section: Potential Relevance To Post-traumatic Stressmentioning

confidence: 99%

“…The ability to extinguish intense aversive memories is of significant clinical interest, in particularly concerning phobias, panic disorder, and post-traumatic stress disorder (PTSD) (Charney et al, 1993;Davis and Myers, 2002;Fyer, 1998;Gorman et al, 2000). Converging evidence indicates that the amygdala plays an important role in emotional conditioning and its experimental extinction (Davis, 1992;Falls et al, 1992;LeDoux, 1993;Lu et al, 2001;Maren, 1999;McGaugh et al, 1993;Nader et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

NMDA Partial Agonist Reverses Blocking of Extinction of Aversive Memory by GABAA Agonist in the Amygdala

Akirav

2006

Neuropsychopharmacol

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The ability to extinguish aversive memories is of significant clinical interest. The amygdala plays an important role in emotional conditioning and its experimental extinction. It has been suggested that g-aminobutyric acid (GABA) agonists retard extinction and that consolidation of extinction involves N-methyl-D-aspartate receptor (NMDAR)-mediated plasticity. The aim was to further explore the interaction between GABA and NMDA in the amygdala in consolidation of experimental extinction in the rat. To that end conditioned taste aversion (CTA) was used. In CTA, the amygdala has been reported to subserve both acquisition and extinction. The GABA A receptor agonist, muscimol, administered into the amygdala immediately after the first extinction session, caused lasting disruption of extinction of CTA for at least 2 weeks. However, the administration of GABA A receptor antagonists had no effect on extinction kinetics. Microinfusing the partial NMDA agonist D-cycloserine together with or after muscimol infusion reversed the blocking effects of muscimol. These findings could bear relevance to the potential involvement of extinction abnormalities in behavioral disorders, and their amelioration.

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“…Na resposta aguda ao estresse, há um aumento importante de noradrenalina na fenda sináptica, resultando num aumento da resposta monosináptica evocada. 8 Com relação à dopamina, o estresse aumenta a liberação e o metabolismo deste neurotransmissor no córtex pré-frontal, uma área envolvida na produção de respostas ao estresse 9 . O envolvimento da dopamina com estados de hipervigilância já está bem estabelecido.…”

Section: Neurotransmissores E Estresseunclassified

Relação entre estressores, estresse e ansiedade

Margis

Picon

Cosner

et al. 2003

Rev. psiquiatr. Rio Gd. Sul

177

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Os autores apresentam uma breve revisão de literatura sobre a relação entre ansiedade, eventos estressores e estresse. São descritas as diferentes situações estressoras, a definição de evento de vida estressor e os aspectos cognitivos, comportamentais e fisiológicos da resposta frente ao estresse. A neuroanatomia e os principais neurotransmissores envolvidos na resposta fisiológica de ansiedade ao estresse são descritos. Estudos genéticos que evidenciam a relação entre os eventos de vida estressores como fator de risco para ansiedade são apresentados. A relação causal entre os eventos de vida estressores e o aparecimento de ansiedade é abordada a partir de estudos realizados com adultos e adolescentes.

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Psychobiologic Mechanisms of Posttraumatic Stress Disorder

Cited by 567 publications

References 178 publications

Role of the Hippocampus, the Bed Nucleus of the Stria Terminalis, and the Amygdala in the Excitatory Effect of Corticotropin-Releasing Hormone on the Acoustic Startle Reflex

Role of the Hippocampus, the Bed Nucleus of the Stria Terminalis, and the Amygdala in the Excitatory Effect of Corticotropin-Releasing Hormone on the Acoustic Startle Reflex

NMDA Partial Agonist Reverses Blocking of Extinction of Aversive Memory by GABAA Agonist in the Amygdala

Relação entre estressores, estresse e ansiedade

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