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. 2010 Sep;35(10):2134-42.
doi: 10.1038/npp.2010.92. Epub 2010 Jun 30.

Impaired extinction retention in adolescent rats: effects of D-cycloserine

Jessica McCallum  1 , Jee Hyun Kim, Rick Richardson
Affiliations

Impaired extinction retention in adolescent rats: effects of D-cycloserine

Jessica McCallum et al. Neuropsychopharmacology. 2010 Sep.

Abstract

The developmental trajectory of the prefrontal cortex (PFC) in both rats and humans is nonlinear, with a notable decline in synaptic density during adolescence, potentially creating a 'natural lesion' preparation at this age. Given that the PFC is critically involved in retention of extinction of learned fear in adult humans and rodents, the present study examined whether adolescent rats exhibit impaired extinction retention. The results of experiment 1 showed that adolescent rats were impaired in extinction retention, compared with both younger and older rats. The partial NMDA receptor agonist D-cycloserine (DCS) improved extinction retention in adolescent rats (experiment 2), but only if administered immediately after extinction training (experiment 3). In addition, providing extended extinction training improved extinction retention in adolescent rats in a manner similar to that of DCS (experiment 4). The results of this study show that adolescent rats exhibit impaired extinction retention, and that this can be reduced through either DCS or extended extinction training. These novel findings have potential implications for clinical treatments of fear and anxiety disorders in adolescent patients.

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Figures

Figure 1
Figure 1
(a) The training protocol for experiment 1, with each arrow indicating 1 day. Mean (±SEM) percentage of CS-elicited freezing is shown for each group at training (b), extinction (c), and test (d) in experiment 1. Rats (35 days old) show impaired extinction retention (ie, higher levels of freezing) at test compared with 24- and 70-day-old rats.
Figure 2
Figure 2
(a) The training protocol for experiment 2, with each arrow indicating 1 day, with the exception of the interval between extinction and injection, which was 10 minutes. Mean (±SEM) percentage of CS-elicited freezing is shown for each group at training (b), extinction (c), and test (d) in experiment 2. A high dose of DCS resulted in significantly less freezing at test compared with saline in adolescent rats.
Figure 3
Figure 3
(a) The training protocol for experiment 3, with each arrow indicating 1 day, unless otherwise indicated. Mean (±SEM) percentage of CS-elicited freezing is shown for each group at training (b), extinction (c), and test (d) in experiment 3. Immediate injection of DCS resulted in significantly less freezing at test compared with the saline control group in adolescent rats. However, a 4 h delayed injection of DCS resulted in no difference compared with the saline control group.
Figure 4
Figure 4
(a) The training protocol for experiment 4, with each arrow indicating 1 day, unless otherwise indicated. Mean (±SEM) percentage of CS-elicited freezing is shown for each group at training (b), extinction (c), and test (d) in experiment 4. Adolescent rats in the saline control group exhibited significantly higher levels of freezing at test compared with rats given DCS after extinction, and rats given no injection but double the extinction training. There were no differences between the DCS and extended extinction groups.
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