Mild prenatal stress-modulated behavior and neuronal spine density without affecting amphetamine sensitization.

The present study investigated the effect of prenatal stress (PS) on juvenile behavior and adult amphetamine (AMPH) sensitization, as well as the effect of the interaction between experience (i.e. PS) and drug (i.e. AMPH) on cortical thickness and neuronal morphology in corticolimbic regions in rats. Juvenile male and female rats, exposed to gestational stress, were tested in behavioral tasks that included open field locomotion, elevated plus maze, novel object recognition, and play fighting behavior. The development and persistence of drug-induced behavioral sensitization in adults were tested by chronic AMPH administration and challenge, respectively. Spine density in corticolimbic regions was examined for structural plasticity. The findings showed that PS produced anxiety-like behavior in males. Furthermore, PS in males resulted in female-like play and enhanced partial rotation defense, whereas in females PS increased the probability of evasion in response to an attack. AMPH administration resulted in gradual increase in behavioral sensitization that persisted at least for 2 weeks; however, PS did not influence AMPH-induced behavioral sensitization in either male or female rats. Moreover, PS increased the spine density in the nucleus accumbens (NAc) and decreased it in the medial prefrontal cortex (mPFC) without any alteration in the orbital frontal cortex (OFC). Similarly, AMPH administration increased spine density in the NAc and mPFC, whereas a decrease was observed in the OFC. However, PS prevented the drug-induced alterations in the spine density observed in controls. In sum, PS modulated juvenile behavior and altered brain morphology without influencing AMPH-induced behavioral sensitization substantially.