Impaired Extinction Retention in Adolescent Rats: Effects of D-Cycloserine

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. Neuropsychopharmacology (2010) 35, 2134-2142; doi:10.1038/npp.2010.92; published online 30 June 2010