Early-life experience with impoverished or enriching environmental factors can affect later life. In our study, environmental manipulations (social isolation and chronic handling), performed from weaning to adulthood, spanned the critical developmental period of adolescence in rodents. During adolescence, key neurotransmitter systems (e.g., endocannabinoid, glutamate, dopamine) undergo maturation (Spear, 2000, Galve-Roperh et al., 2009) and positive events may either facilitate future adaptations (Boyce and Ellis, 2005) or counteract consequences of negative events (Laviola et al., 2008). The efficacy of the manipulations used here to alter both behavioral reactivity to context (see Fig. 1) and the endocannabinoid system (for summary see Fig. 9) may be attributed to the elevated susceptibility of rodents to environmental manipulations occurring during this developmental window.