Role of brain‐derived neurotrophic factor in the ventral tegmental area in social stress‐induced psychomotor sensitization using virus‐mediated gene‐transfer

Abstract

Brain‐derived neurotrophic factor (BDNF) is a known mediator of brain plasticity and is produced by dopamine neurons in the ventral tegmental area (VTA). The VTA is involved in the reinforcing effects of abused drugs, and manipulation of VTA BDNF modulates drug‐directed behavior. Sensitization, a progressive increase of locomotor response to successive drug exposures, results from neuroadaptive changes in brain thought to parallel those involved in addiction. Intermittent social stress augments locomotor response to psychostimulants, known as cross‐sensitization. Recently, we found that intermittent social stress increases VTA BDNF, which may be important for adaptations leading to cross‐sensitization. Here we use adeno‐associated virus (AAV)‐mediated gene transfer to alter VTA BDNF in male rats. We show intra‐VTA infusion of AAV‐BDNF or AAV‐siRNA(bdnf) effectively increases or decreases VTA BDNF, respectively, and increases or decreases locomotor response to amphetamine, respectively. In addition, over‐expression of VTA BDNF augmented sensitization after a single stress, and knockdown of VTA BDNF attenuated sensitization after intermittent stress. Taken together, these data indicate that VTA BDNF plays a significant role in persistent sensitization after stress, and may be important for understanding the relationship between stress and addiction