Noradrenergic and Serotonergic Function in Posttraumatic Stress Disorder

Southwick, Steven M.; Krystal, John H.; Bremner, J. Douglas; Morgan, Charles A.; Nicolaou, Andreas L.; Nagy, Linda M.; Johnson, David R.; Heninger, George R.; Charney, Dennis S.

doi:10.1001/archpsyc.1997.01830200083012

Cited by 284 publications

(128 citation statements)

References 79 publications

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“…However, the lack of correlation between these changes suggests that individual differences may influence which neurobiological system is affected in each specific case, and that different subjects within the same diagnostic category may have different response profiles. A recent pharmacological challenge study also suggested the presence of neurobiologically distinct subgroups of PTSD patients (Southwick et al 1997). This is consistent with our suggestion that PTSD patients are not a neurobiologically homogenous group.…”

Section: Resultssupporting

confidence: 92%

Neuroendocrine and Psychophysiologic Responses in PTSD: A Symptom Provocation Study

Liberzon

Abelson

Flagel

et al. 1999

Neuropsychopharmacology

254

142

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Section: Resultssupporting

confidence: 92%

Neuroendocrine and Psychophysiologic Responses in PTSD: A Symptom Provocation Study

Liberzon

Abelson

Flagel

et al. 1999

Neuropsychopharmacology

254

142

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“…PTSD patients exhibit a resistance to extinction (Orr et al, 2000) and NE hyperresponsiveness to traumatic stimuli (Geracioti et al, 2006), suggesting that NE hyperresponsiveness may be responsible for impairing extinction learning. Yohimbine, which causes NE hyperresponsiveness, can induce panic attacks in PTSD patients (Southwick et al, 1997(Southwick et al, , 1999). In contrast, we found that extinction is dependent on activation of noradrenergic ␤-receptors in IL.…”

Section: Discussionmentioning

confidence: 99%

Noradrenergic Signaling in Infralimbic Cortex Increases Cell Excitability and Strengthens Memory for Fear Extinction

Mueller¹,

Porter²,

Quirk³

2008

J. Neurosci.

263

197

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Emotional arousal strengthens memory. This is most apparent in aversive conditioning, in which the stress-related neurotransmitter norepinephrine (NE) enhances associations between sensory stimuli and fear-inducing events. In contrast to conditioning, extinction decreases fear responses, and is thought to form a new memory. It is not known, however, whether NE is necessary for extinction learning. Previous work has shown that the infralimbic prefrontal cortex (IL) is a site of extinction consolidation. Here, we show that blocking noradrenergic ␤-receptors in IL before extinction training impaired retrieval of extinction the following day, consistent with a weakened extinction memory. We further found that the sequelae of ␤-receptor activation, including protein kinase A (PKA), gene transcription and translation in IL, are necessary for extinction. To determine whether activation of this cascade modulates IL excitability, we measured the response of IL pyramidal neurons to injected current. NE increased the excitability of IL neurons in a ␤-receptor-and PKA-dependent manner. We suggest that NE released in IL during fear extinction activates a PKA-mediated molecular cascade that strengthens extinction memory. Thus, emotional arousal evoked by conditioned fear paradoxically promotes the subsequent extinction of that fear, thereby ensuring behavioral flexibility.

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“…Norepinephrine (NE) not only plays an important role in mood and arousal, but also in the encoding, retrieval, and reconsolidation of emotional memories (9)(10)(11)(12)(13). Endogenous NE signaling is elevated in PTSD and drugs that block NE receptors are already being used with some success to either prevent or treat PTSD, including its symptoms of hyperarousal and nightmares (14)(15)(16)(17)(18). Clinically effective noradrenergic drugs include the α1-adrenoceptor antagonist, prazosin, and the β1/β2-adrenoceptor antagonist, propranolol (17,(19)(20)(21).…”

mentioning

confidence: 99%

Noradrenergic blockade stabilizes prefrontal activity and enables fear extinction under stress

Fitzgerald

Giustino

Seemann

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

117

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Stress-induced impairments in extinction learning are believed to sustain posttraumatic stress disorder (PTSD). Noradrenergic signaling may contribute to extinction impairments by modulating medial prefrontal cortex (mPFC) circuits involved in fear regulation. Here we demonstrate that aversive fear conditioning rapidly and persistently alters spontaneous single-unit activity in the prelimbic and infralimbic subdivisions of the mPFC in behaving rats. These conditioning-induced changes in mPFC firing were mitigated by systemic administration of propranolol (10 mg/kg, i.p.), a β-noradrenergic receptor antagonist. Moreover, propranolol administration dampened the stress-induced impairment in extinction observed when extinction training is delivered shortly after fear conditioning. These findings suggest that β-adrenoceptors mediate stress-induced changes in mPFC spike firing that contribute to extinction impairments. Propranolol may be a helpful adjunct to behavioral therapy for PTSD, particularly in patients who have recently experienced trauma.fear | extinction | propranolol | prefrontal cortex | rat

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Noradrenergic and Serotonergic Function in Posttraumatic Stress Disorder

Abstract: These data suggest the presence of 2 neurobiological subgroups of patients with PTSD, one with a sensitized noradrenergic system, and the other with a sensitized serotonergic system.

Cited by 284 publications

References 79 publications

Neuroendocrine and Psychophysiologic Responses in PTSD: A Symptom Provocation Study

Neuroendocrine and Psychophysiologic Responses in PTSD: A Symptom Provocation Study

Noradrenergic Signaling in Infralimbic Cortex Increases Cell Excitability and Strengthens Memory for Fear Extinction

Noradrenergic blockade stabilizes prefrontal activity and enables fear extinction under stress

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