This study investigated the effect of postnatal tactile stimulation (TS) on juvenile behavior, adult amphetamine (AMPH) sensitization, and the interaction of TS and AMPH on prefrontal cortical (PFC) thickness and striatum size. Pups received TS by stroking daily with a feather duster from birth till weaning and were tested, as juveniles, in behavioral tasks including open field locomotion, elevated maze, novel object recognition, and play fighting behavior. Development and persistence of drug-induced behavioral sensitization was tested by chronic AMPH administration and challenge, respectively. PFC thickness and striatum size were assessed from serial brain sections. The findings showed that TS rats spent less time with novel objects on first exposure but open field locomotion and elevated plus maze tasks were not affected substantially. TS reduced the frequency of play fighting and enhanced evasion in response to a playful attack, but only in males. The probability of complete rotation defense, leading to a supine posture during play, was reduced in both sexes. AMPH administration resulted in gradual increase in behavioral sensitization that persisted at least for 2 weeks. However, TS rats exhibited attenuated AMPH sensitization compared to sex-matched controls. Neuroanatomically, AMPH reduced the PFC thickness in control females but enlarged the posterior striatum in control males. TS experience blocked these effects. In summary, TS during development modulated the response to novel objects and altered social behaviors and attenuated AMPH-induced behavioral sensitization by preventing drug-induced structural alteration in the PFC and the striatum, brain regions implicated in drug abuse. © 2011 American Psychological Association.