The Neurochemical Mechanisms of the Pharmacological Activities of Inverse Agonists of the Benzodiazepine Binding Site

Golovko, A. I.; Иванов, М. Б.; Golovko, E. S.; Dolgo-Saburov, V. B.; Zatsepin, E. P.

doi:10.1134/s1819712418030042

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(2 citation statements)

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“…(1) explore the neurobiology of memory; (2) allow testing of manipulations that may improve episodic memory in these patients (Golovko et al, 2018), who are unlikely to be available in sufficient number to enable controlled experimental designs; and (3) manipulate priorly consolidated memories (see Makkar et al, 2010;Walsh et al, 2018) brought to mind (reactivated) under BZ effects, especially memories related to anxiety and depression symptoms which are modulated by the BZ receptor system (see Prevot et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

“…This is especially true considering the renewed interest in manipulations of the BZ receptor system as a potential target for clinical applications that involve changes in memory. Examples are recent findings that some BZ inverse agonists exhibit pro-cognitive (Golovko, Ivanov, Golovko, Dolgo-saburov, & Zatsepin, 2018), antianxiety and antidepressant effects (Prevot et al, 2019). Additionally, the possibility of editing unwanted episodic memories with the use of drugs seems to hold great promise (Gravitz, 2019;Phelps & Hofmann, 2019).…”

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confidence: 99%

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A reappraisal of acute doses of benzodiazepines as a model of anterograde amnesia

Segura

McGhee

Sala

et al. 2020

Human Psychopharmacology

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Objective: Acute administration of benzodiazepines is considered a pharmacological model of general organic anterograde amnesias (OAA). We sought to determine which type of amnesia these drugs best model by comparing the effects of diazepam with those reported in amnesiacs regarding working memory capacity (WMC), susceptibility to retroactive interference (RI), and accelerated forgetting. Methods:In this double-blind, parallel-group design study, 30 undergraduates were randomly allocated to acute oral treatments with 15 mg diazepam or placebo. WMC and story recall were assessed pre-and post-treatment. Story presentation was succeeded by 10 min of RI (spotting differences in pictures) or minimal RI (doing nothing in a darkened room). Delayed story recall was assessed under diazepam and 7 days later in a drug-free session to assess accelerated forgetting.Results: Recall of stories encoded under diazepam, whether reactivated or not, was severely impaired (anterograde amnesia). However, diazepam did not impair WMC, increase susceptibility to RI, or accelerate forgetting.Conclusions: Diazepam's amnestic effects mirror those in patients with probable severe medial temporal damage, mostly restricted to initial consolidation and differ from other OAA (Korsakoff syndrome, frontal, transient epileptic, posttraumatic amnesia, and most progressive amnesias) in terms of WMC, susceptibility to RI and accelerated forgetting.

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