Age-related differences in amphetamine sensitization: Effects of prior drug or stress history on stimulant sensitization in juvenile and adult rats

Repeated intermittent exposure to stimulants progressively increases a drug's effect, with stressors capable of producing cross-sensitization to stimulants. Studies examining such sensitization during development are few, however, with results mixed. In Experiment 1, juvenile (P22) and adult (P64) female Sprague–Dawley rats were administered (daily for 4 days) 1.5 mg/kg or 3.0 mg/kg amphetamine (1.5A and 3.0A groups), or saline (SAL group). In a second experiment, rats were exposed to either repeated restraint (60 min/day for 4 days; RS group) or were left non-manipulated in the home cage (NM group). Animals from both experiments were then challenged with 1.5 mg/kg of amphetamine and sensitization assessed via locomotion and stereotypy after a 2-day and 3-wk washout period. When compared to SAL animals, 3.0A juveniles and adults exhibited evidence of locomotor sensitization 2 days post-drug exposure, but this sensitization did not persist to the 3-week challenge. Compared to NM animals, RS animals showed stress-induced locomotor sensitization both 2 days and 3 weeks post-stress exposure, regardless of age. These results demonstrate that repeated drug/stress exposures prior to stimulant challenge are sufficient to induce behavioral sensitization among both juveniles and adults, with these effects particularly long-lasting following repeated stressor exposure.