Pilot study of the effect of lipophilic vs. hydrophilic beta-adrenergic blockers being taken at time of intracardiac defibrillator discharge on subsequent PTSD symptoms

Bhuvaneswar, Chaya G.; Ruskin, Jeremy N.; Katzman, Anna Roglieri; Wood, N.; Pitman, Roger K.

doi:10.1016/j.nlm.2013.12.013

Cited by 12 publications

(8 citation statements)

References 32 publications

(33 reference statements)

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“…At least one key aspect, namely the interval between trauma exposure and administration of this drug (immediately vs. ≥ 6h), may account for this apparent divergence. Indeed, it is able to attenuate the PTSD outcome when administrated at the time of discharging a highly stressful stimulus capable of inducing PTSD features in humans ( Bhuvaneswar et al, 2014 ).…”

Section: Discussionmentioning

confidence: 99%

PTSD-Like Memory Generated Through Enhanced Noradrenergic Activity is Mitigated by a Dual Step Pharmacological Intervention Targeting its Reconsolidation

Gazarini

Stern

Piornedo

et al. 2014

International Journal of Neuropsychopharmacology

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Background:Traumatic memories have been resilient to therapeutic approaches targeting their permanent attenuation. One of the potentially promising pharmacological strategies under investigation is the search for safe reconsolidation blockers. However, preclinical studies focusing on this matter have scarcely addressed abnormal aversive memories and related outcomes.Methods:By mimicking the enhanced noradrenergic activity reported after traumatic events in humans, here we sought to generate a suitable condition to establish whether some clinically approved drugs able to disrupt the reconsolidation of conditioned fear memories in rodents would still be effective.Results:We report that the α2-adrenoceptor antagonist yohimbine was able to induce an inability to restrict behavioral (fear) and cardiovascular (increased systolic blood pressure) responses to the paired context when administered immediately after acquisition, but not 6h later, indicating the formation of a generalized fear memory, which endured for over 29 days and was less susceptible to suppression by extinction. It was also resistant to reconsolidation disruption by the α2-adrenoceptor agonist clonidine or cannabidiol, the major non-psychotomimetic component of Cannabis sativa. Since signaling at N-methyl-D-aspartate (NMDA) receptors is important for memory labilization and because a dysfunctional memory may be less labile than is necessary to trigger reconsolidation on its brief retrieval and reactivation, we then investigated and demonstrated that pre-retrieval administration of the partial NMDA agonist D-cycloserine allowed the disrupting effects of clonidine and cannabidiol on reconsolidation.Conclusions:These findings highlight the effectiveness of a dual-step pharmacological intervention to mitigate an aberrant and enduring aversive memory similar to that underlying the post-traumatic stress disorder.

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Section: Discussionmentioning

confidence: 99%

PTSD-Like Memory Generated Through Enhanced Noradrenergic Activity is Mitigated by a Dual Step Pharmacological Intervention Targeting its Reconsolidation

Gazarini

Stern

Piornedo

et al. 2014

International Journal of Neuropsychopharmacology

View full text Add to dashboard Cite

show abstract

“…Sometimes acute pain can constitute the traumatic event, such as in a case of traumatic eye enucleation, 37 and in cases of implantable cardioverter defibrillator discharges. 38 PTSD also appears to permit induction of an opioid-mediated, stress-induced analgesia. PTSD-related stimuli can result in a naloxone-reversible decreased sensitivity to noxious stimuli in affected individuals.…”

Section: Posttraumatic Stress Disordermentioning

confidence: 99%

Psychiatric and Psychological Perspectives on Chronic Pain

Howe

Robinson

Sullivan

2015

Physical Medicine and Rehabilitation Clinics of North America

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“…10 This study demonstrated that, if taken in the aftermath of the shock, lipophilic beta blockers (e.g., propranolol, metoprolol, and carvedilol) are more effective at reducing later PTSD symptoms than their hydrophilic counterparts (e.g., atenolol and sotalol), likely owing to the lipophilic drug's ability to pass the blood-brain barrier. Thus, lipophilic beta blockers may have a significant role in reducing PTSD symptoms in patients with AICDs.…”

Section: Discussionmentioning

confidence: 78%