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Basolateral amygdala corticotropin releasing factor receptor 2 interacts with nonmuscle myosin II to destabilize memory in males.
Hafenbreidel, Madalyn; Pandey, Surya; Briggs, Sherri B; Arza, Meghana; Bonthu, Shalakha; Fisher, Cadence; Tiller, Annika; Hall, Alice B; Reed, Shayna; Mayorga, Natasha; Lin, Li; Khan, Susan; Cameron, Michael D; Rumbaugh, Gavin; Miller, Courtney A.
Afiliação
  • Hafenbreidel M; Department of Molecular Medicine, The Scripps Research Institute, Jupiter, FL 33458, United States; Department of Neuroscience, The Scripps Research Institute, Jupiter, FL 33458, United States; The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology, Jupiter, FL 33458, U
  • Pandey S; Department of Molecular Medicine, The Scripps Research Institute, Jupiter, FL 33458, United States; Department of Neuroscience, The Scripps Research Institute, Jupiter, FL 33458, United States; The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology, Jupiter, FL 33458, U
  • Briggs SB; Department of Molecular Medicine, The Scripps Research Institute, Jupiter, FL 33458, United States; Department of Neuroscience, The Scripps Research Institute, Jupiter, FL 33458, United States; The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology, Jupiter, FL 33458, U
  • Arza M; Department of Molecular Medicine, The Scripps Research Institute, Jupiter, FL 33458, United States; Department of Neuroscience, The Scripps Research Institute, Jupiter, FL 33458, United States; The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology, Jupiter, FL 33458, U
  • Bonthu S; Department of Molecular Medicine, The Scripps Research Institute, Jupiter, FL 33458, United States; Department of Neuroscience, The Scripps Research Institute, Jupiter, FL 33458, United States; The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology, Jupiter, FL 33458, U
  • Fisher C; Department of Molecular Medicine, The Scripps Research Institute, Jupiter, FL 33458, United States; Department of Neuroscience, The Scripps Research Institute, Jupiter, FL 33458, United States; The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology, Jupiter, FL 33458, U
  • Tiller A; Department of Molecular Medicine, The Scripps Research Institute, Jupiter, FL 33458, United States; Department of Neuroscience, The Scripps Research Institute, Jupiter, FL 33458, United States; The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology, Jupiter, FL 33458, U
  • Hall AB; Department of Molecular Medicine, The Scripps Research Institute, Jupiter, FL 33458, United States; Department of Neuroscience, The Scripps Research Institute, Jupiter, FL 33458, United States; The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology, Jupiter, FL 33458, U
  • Reed S; Department of Molecular Medicine, The Scripps Research Institute, Jupiter, FL 33458, United States; Department of Neuroscience, The Scripps Research Institute, Jupiter, FL 33458, United States; The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology, Jupiter, FL 33458, U
  • Mayorga N; Department of Molecular Medicine, The Scripps Research Institute, Jupiter, FL 33458, United States; Department of Neuroscience, The Scripps Research Institute, Jupiter, FL 33458, United States; The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology, Jupiter, FL 33458, U
  • Lin L; Department of Molecular Medicine, The Scripps Research Institute, Jupiter, FL 33458, United States; The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology, Jupiter, FL 33458, United States.
  • Khan S; Department of Molecular Medicine, The Scripps Research Institute, Jupiter, FL 33458, United States; The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology, Jupiter, FL 33458, United States.
  • Cameron MD; Department of Molecular Medicine, The Scripps Research Institute, Jupiter, FL 33458, United States; The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology, Jupiter, FL 33458, United States.
  • Rumbaugh G; Department of Neuroscience, The Scripps Research Institute, Jupiter, FL 33458, United States; The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology, Jupiter, FL 33458, United States.
  • Miller CA; Department of Molecular Medicine, The Scripps Research Institute, Jupiter, FL 33458, United States; Department of Neuroscience, The Scripps Research Institute, Jupiter, FL 33458, United States; The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology, Jupiter, FL 33458, U
Neurobiol Learn Mem ; 206: 107865, 2023 Dec.
Article em En | MEDLINE | ID: mdl-37995804
Preclinical studies show that inhibiting the actin motor ATPase nonmuscle myosin II (NMII) with blebbistatin (Blebb) in the basolateral amgydala (BLA) depolymerizes actin, resulting in an immediate, retrieval-independent disruption of methamphetamine (METH)-associated memory in male and female adult and adolescent rodents. The effect is highly selective, as NMII inhibition has no effect in other relevant brain regions (e.g., dorsal hippocampus [dPHC], nucleus accumbens [NAc]), nor does it interfere with associations for other aversive or appetitive stimuli, including cocaine (COC). To understand the mechanisms responsible for drug specific selectivity we began by investigating, in male mice, the pharmacokinetic differences in METH and COC brain exposure . Replicating METH's longer half-life with COC did not render the COC association susceptible to disruption by NMII inhibition. Therefore, we next assessed transcriptional differences. Comparative RNA-seq profiling in the BLA, dHPC and NAc following METH or COC conditioning identified crhr2, which encodes the corticotropin releasing factor receptor 2 (CRF2), as uniquely upregulated by METH in the BLA. CRF2 antagonism with Astressin-2B (AS2B) had no effect on METH-associated memory after consolidation, allowing for determination of CRF2 influences on NMII-based susceptibility. Pretreatment with AS2B prevented the ability of Blebb to disrupt an established METH-associated memory. Alternatively, combining CRF2 overexpression and agonist treatment, urocortin 3 (UCN3), in the BLA during conditioning rendered COC-associated memory susceptible to disruption by NMII inhibition, mimicking the Blebb-induced, retrieval-independent memory disruption seen with METH. These results suggest that BLA CRF2 receptor activation during memory formation in male mice can prevent stabilization of the actin-myosin cytoskeleton supporting the memory, rendering it vulnerable to disruption by NMII inhibition. CRF2 represents an interesting target for BLA-dependent memory destabilization via downstream effects on NMII.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Cocaína / Receptores de Hormônio Liberador da Corticotropina / Complexo Nuclear Basolateral da Amígdala / Metanfetamina Limite: Animals Idioma: En Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Cocaína / Receptores de Hormônio Liberador da Corticotropina / Complexo Nuclear Basolateral da Amígdala / Metanfetamina Limite: Animals Idioma: En Ano de publicação: 2023 Tipo de documento: Article