Behavioural Brain Research 264 (2014) 161–172 Contents lists available at ScienceDirect Behavioural Brain Research jou rn al hom epage: www.elsevier.com/locate/bbr Research report The effects of early-life adversity on fear memories in adolescent rats and their persistence into adulthood Agnieszka Chocyk a,∗ , Aleksandra Przyborowska a , Wioletta Makuch b , Iwona Majcher-Ma ´ slanka a , Dorota Dudys a , Krzysztof W˛ edzony a a Laboratory of Pharmacology and Brain Biostructure, Institute of Pharmacology, Polish Academy of Sciences, 12 Smetna Street, 31-343 Krakow, Poland b Department of Pain Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, 12 Smetna Street, 31-343 Krakow, Poland h i g h l i g h t s • Maternal separation (MS) decreases the expression of learned fear in adolescents. • MS-induced impairments of fear conditioning persist into adulthood. • MS may increase the risk for early- and late-onsets psychopathologies. a r t i c l e i n f o Article history: Received 4 August 2013 Received in revised form 27 January 2014 Accepted 28 January 2014 Available online 4 February 2014 Keywords: Adolescence Auditory fear conditioning Contextual fear conditioning Early-life stress Fear extinction Maternal separation a b s t r a c t Adolescence is a developmental period characterized by extensive morphological and functional remod- eling of the brain. The processes of brain maturation during this period may unmask malfunctions that originate earlier in life as a consequence of early-life stress (ELS). This is associated with the emergence of many psychopathologies during adolescence, particularly affective spectrum disorders. In the present study, we applied a maternal separation (MS) procedure (3 h/day, on postnatal days 1–14) as a model of ELS to examine its effects on the acquisition, expression and extinction of fear memories in adoles- cent rats. Additionally, we studied the persistence of these memories into adulthood. We found that MS decreased the expression of both contextual (CFC) and auditory (AFC) fear conditioning in adolescent rats. Besides, MS had no impact on the acquisition of extinction learning. During the recall of extinction MS animals both, those previously subjected and not subjected to the extinction session, exhibited equally low levels of freezing. In adulthood, the MS animals (conditioned during adolescence) still displayed impairments in the expression of AFC (only in males) and CFC. Furthermore, the MS procedure had also an impact on the expression of CFC (but not AFC) after retraining in adulthood. Our findings imply that ELS may permanently affect fear learning and memory. The results also support the hypothesis that, depending on individual predispositions and further experiences, ELS may either lead to a resilience or a vulnerability to early- and late-onsets psychopathologies. © 2014 Elsevier B.V. All rights reserved. 1. Introduction Fear memory is an important acquired ability that allows an organism to predict and avoid aversive events. Acquisition of fear memory (i.e., fear conditioning: FC) is a process in which humans and animals learn that usually neutral sensory information gains a value as predictor of danger or probability of an aversive situ- ation. In functional terms, such fear memories help to minimize exposure to threat and elicit escape and/or avoidance responses [1]. ∗ Corresponding author at: 12 Smetna Street, 31-343 Krakow, Poland. Tel.: +48 12 6623 229; fax: +48 12 637 45 00. E-mail address: chocyk@if-pan.krakow.pl (A. Chocyk). When fear memory traces are formed with inappropriate strength or duration, they may lead to malfunction of behavioral adjust- ment to life demands and challenges. For example, if the traces of fear memories are too weak, this condition may lead to engage- ment in life-threatening or risky actions. On the other hand, if the fear response is over-generalized and/or fear memories excessively strong, this state may result in anxiety disorders such as phobias, panic disorders or posttraumatic stress disorder (PTSD) [1]. The neural circuits involved in the regulation of fear responses and fear memory formation are evolutionarily conserved; thus, the mechanisms of fear learning can be successfully studied in both humans and laboratory animals using various behavioral paradigms [2,3]. One of the most frequently applied behavioral paradigms is classical (Pavlovian) FC. In classical conditioning, a 0166-4328/$ – see front matter © 2014 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.bbr.2014.01.040