Effects of withdrawal from repeated amphetamine exposure in peri-puberty on neuroplasticity-related genes in mice

Abstract

Although extensive evidence demonstrates that repeated administration of amphetamine (AMPH) induces behavioral and neurochemical sensitization, the influence of the developmental timing of AMPH administration is unknown. This is an important issue to address because it could help clarify the influence of early drug exposure on neuronal plasticity and the involvement of dopaminergic sensitization in the etiopathology of neuropsychiatric disorders.Thus, we decided to investigate the molecular alterations induced by the administration of AMPH during adolescence, when repeated exposure to the psychostimulant may interfere with developmental neuroplasticity. We investigated the expression of the neurotrophin brain-derived neurotrophic factor (BDNF) and of two inducible-early genes (arc and cfos) that bridge neuronal activity with long-lasting functional alterations. We found that peri-pubertal treatment with AMPH induces long-lasting changes in the expression of bdnf and of activity-regulated genes in the hippocampus and in the prefrontal/frontal cortex, and leads to alterations of their short-term modulation in response to a subsequent acute AMPH challenge. These data suggest that AMPH exposure in peri-puberty may negatively affect the maturation of brain structures, such as the prefrontal cortex, which facilitate the development of dopamine sensitization and may contribute to dopamine-dependent behavioral dysfunctions and molecular alterations in adulthood.