A comparison of the short- and long-term effects of corticosterone exposure on extinction in adolescence versus adulthood.

Abstract

Human and nonhuman adolescents have impaired retention of extinction of learned fear, relative to juveniles and adults. It is unknown whether exposure to stress affects extinction differently in adolescents versus adults. These experiments compared the short- and long-term effects of exposure to the stress-related hormone corticosterone (CORT) on the extinction of learned fear in adolescent and adult rats. Across all experiments, adolescent and adult rats were trained to exhibit good extinction retention by giving extinction training across 2 consecutive days. Despite this extra training, adolescents exposed to 1 week of CORT (200 μg/ml) in their drinking water showed impaired extinction retention when trained shortly after the CORT was removed (Experiment 1a). In contrast, adult rats exposed to CORT (200 μg/ml) for the same duration did not exhibit deficits in extinction retention (Experiment 1b). Exposing adolescents to half the amount of CORT (100 μg/ml; Experiment 1c) for 1 week similarly disrupted extinction retention. Extinction impairments in adult rats were only observed after 3 weeks, rather than 1 week, of CORT (200 μg/ml; Experiment 1d). Remarkably, however, adult rats showed impaired extinction retention if they had been exposed to 1 week of CORT (200 μg/ml) during adolescence (Experiment 2). Finally, exposure to 3 weeks of CORT (200 μg/ml) in adulthood led to long-lasting extinction deficits after a 6-week drug-free period (Experiment 3). These findings suggest that although CORT disrupts both short- and long-term extinction retention in adolescents and adults, adolescents may be more vulnerable to these effects because of the maturation of stress-sensitive brain regions. (PsycINFO Database Record (c) 2014 APA, all rights reserved).

Differences in the persistence of spatial memory deficits induced by a chronic stressor in adolescents compared to juveniles

“…In contrast, those exposed to the same treatment during the juvenile period demonstrated intact spatial memory 6 weeks after treatment. These results align with other studies that have shown that another form of learning, namely fear extinction retention, is affected more by chronic Cort exposure that occurs during adolescence as opposed to adulthood or during the juvenile period (Den et al, ; Stylianakis, Richardson, & Baker, ). Second, our study also demonstrates that exposure to ethanol or Cort in either the juvenile or adolescent period impairs hippocampally dependent place memory shortly (i.e., 6 days) after exposure to the treatment.…”

“…As noted earlier, we found that, after a 6‐day washout period, animals exposed to Cort or to the ethanol vehicle displayed impaired spatial memory, regardless of whether that exposure occurred during the juvenile period or adolescence. Although we did not observe any behavioral effect of an even higher dose of ethanol (5%) after a similar washout period in a previous study on fear conditioning and extinction in adolescent rats (Den et al, ), the current findings fit with several reports of ethanol impairing hippocampally dependent memory in adolescent rats (e.g., Hunt & Barnet, ; Markwiese, Acheson, Levin, Wilson, & Swartzwelder, ; Sircar, Basak, & Sircar, ; White, Ghia, Levin, & Swartzwelder, ). Furthermore, to our knowledge, no previous studies have examined the effect of juvenile ethanol exposure on spatial memory, although there is evidence that ethanol exposure across infant and juvenile ages (from P15‐P25) impairs N ‐methyl‐ d ‐aspartate receptor‐mediated postsynaptic potentials and long‐term potentiation in the hippocampus, with this effect observed to a smaller degree in adult rats (Swartzwelder, Wilson, & Tayyeb, ).…”

“…There were three treatment groups in this experiment: corticosterone (Cort), vehicle (Veh), and water. Animals in the Cort condition were given 200 μg/ml of Cort in their drinking water (Catalani et al, ; Den, Altmann, & Richardson, ). The Cort was dissolved in 2.5% ethanol and therefore we included a vehicle group that received 2.5% ethanol in their drinking water.…”

Elucidating the mechanisms of fear extinction in developing animals: a special case of NMDA receptor-independent extinction in adolescent rats

“…Typically, rats conditioned and extinguished as adolescents exhibit impaired extinction retention when given the same amount of extinction training (i.e., 30 trials) as occurred in Experiment 1 (e.g., McCallum et al 2010). When rats conditioned as adolescents receive extended extinction training (e.g., 2 d, 30 trials per day), this leads to improved extinction retention (Den et al 2014;Baker and Richardson 2017). Further, adolescent rats recruit NMDARs under these conditions, as systemic administration of MK801 prior to the second extinction session blocks this improvement in extinction retention (Baker and Richardson 2017).…”

Individual differences in fear extinction and anxiety-like behavior

“…Subjects in the vehicle/control condition were given water with 5% ethanol. Animals were exposed to altered drinking water for 21 d. This procedure is consistent with previous experiments that have exposed rats to CORT (e.g., Den et al 2014).…”