title: Evidence for an expanded time-window to mitigate a reactivated fear memory by tamoxifen.
abstract: The mechanisms underpinning the persistence of emotional memories are inaccurately understood. Advancing the current level of understanding with regards to this aspect is of potential translational value for the treatment of post-traumatic stress disorder (PTSD), which stems from an abnormal aversive memory formation. Tamoxifen (TMX) is a drug used in chemotherapy for breast cancer and associated with poor cognitive performances. The present study investigated whether the systemic administration of TMX (1.0-50mg/kg) during and/or beyond the reconsolidation time-window could attenuate a reactivated contextual fear memory in laboratory animals. When administered 0, 6 or 9h (but not 12h) post-memory retrieval and reactivation, TMX (50mg/kg) reduced the freezing behavior in male rats re-exposed to the paired context on day 7, but not on day 1, suggesting a specific impairing effect on memory persistence. Importantly, this effect lasts up to 21 days, but it is prevented by omitting the memory retrieval or memory reactivation. When female rats in the diestrous or proestrous phase were used, the administration of TMX 6h after retrieving and reactivating the fear memory also impaired its persistence. Altogether, regardless of the gender, the present results indicate that the TMX is able to disrupt the persistence of reactivated fear memories in an expanded time-window, which could shed light on a new promising therapeutic strategy for PTSD.
authors.affiliation: Department of Pharmacology, Federal University of Paraná, Curitiba, PR, Brazil.
authors.forename: Thiago R
authors.initials: TR
authors.lastname: da Silva
authors.affiliation: Department of Pharmacology, Federal University of Santa Catarina, Florianopólis, SC, Brazil.
authors.forename: Reinaldo N
authors.initials: RN
authors.lastname: Takahashi
authors.affiliation: Department of Pharmacology, Federal University of Santa Catarina, Florianopólis, SC, Brazil.
authors.forename: Leandro J
authors.initials: LJ
authors.lastname: Bertoglio
authors.affiliation: Department of Pharmacology, Federal University of Paraná, Curitiba, PR, Brazil.
authors.forename: Roberto
authors.initials: R
authors.lastname: Andreatini
authors.affiliation: Department of Pharmacology, Federal University of Paraná, Curitiba, PR, Brazil. Electronic address: cristinastern.cs@gmail.com.
authors.forename: Cristina A J
authors.initials: CA
authors.lastname: Stern
mesh_terms: D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000009:adverse effects*; D003213:Conditioning, Psychological / Q000187:drug effects; D030762:Estrous Cycle / Q000502:physiology; D005239:Fear / Q000523:psychology*; D005260:Female; D008297:Male; D008568:Memory / Q000187:drug effects; D011939:Mental Recall / Q000187:drug effects; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D051381:Rats; D017208:Rats, Wistar; D012727:Sex Characteristics; D013629:Tamoxifen / Q000009:adverse effects*; D013997:Time Factors
chemical_list: D018931:Antineoplastic Agents, Hormonal; D013629:Tamoxifen; D011493:Protein Kinase C
keywords: Memory persistence; Memory reconsolidation; Protein kinase C; Tamoxifen