Stress during the gestational period modifies pups’ emotionality parameters and favors preference for morphine in adolescent rats

• Pups exposed to gestational stress (Gest-S) showed smaller body weight gain.
• Gest-S increased and post-NS decreased pups’ corticosterone plasma levels.
• Gest-S-exposed rats showed increased emotionality and stress-related behaviors.
• Gest-S exposure increased morphine-conditioned place preference.
• Endogenous opiate system may be changed by Gest-S, altering responses to opiate drugs.

Experimental animal studies have shown that early life periods are highly vulnerable to environmental factors, which may exert prolonged impact on HPA axis function and on subsequent neurochemical and behavioral responses in adulthood. Here we evaluated the influence of environmental stressful situations in two different early life stages on stress-related behaviors, and morphine-conditioned place preference (CPP), which is indicative of addiction. While in the gestational stress (Gest-S) dams were exposed to daily sessions of chronic mild stress (CMS) for 2 weeks, in the postnatal stress (post-NS) the offspring were exposed daily to neonatal isolation from postnatal day (PND) 2 to PND 9 for 60 min. Animals exposed to post-NS showed lesser anxiety in different behavioral paradigms (elevated plus maze—EPM and defensive burying test—DBT) as well as increased exploratory behavior (open-field task—OFT), and no preference for morphine in CPP. In contrast, animals exposed to Gest-S showed increased corticosterone plasma levels together with anxiety symptoms and greater preference for morphine following three days of drug withdrawal. Our findings indicate that the gestational period is critical for stress, whose effects may be manifest throughout life. On the other hand, post-NS can trigger neuroadaptations able to overcome emotional consequences of early life. We hypothesized that Gest-S is able to modify responses to opioids along adulthood, which may facilitate development of addiction to these drugs.