Striatal modulation of BDNF expression using micro RNA 124a‐expressing lentiviral vectors impairs ethanol‐induced conditioned‐place preference and voluntary alcohol consumption

Alcohol abuse is a major health, economic and social concern in modern societies, but the exact molecular mechanisms underlying ethanol addiction remain elusive. Recent findings show that small non‐coding micro RNA (mi RNA ) signaling contributes to complex behavioral disorders including drug addiction. However, the role of mi RNA s in ethanol‐induced conditioned‐place preference ( CPP ) and voluntary alcohol consumption has not yet been directly addressed. Here, we assessed the expression profile of mi R 124a in the dorsal striatum of rats upon ethanol intake. The results show that mi R 124a was downregulated in the dorso‐lateral striatum ( DLS ) following alcohol drinking. Then, we identified brain‐derived neurotrophic factor ( BDNF ) as a direct target of mi R 124a. In fact, BDNF m RNA was upregulated following ethanol drinking. We used lentiviral vector ( LV ) gene transfer technology to further address the role of mi R 124a and its direct target BDNF in ethanol‐induced CPP and alcohol consumption. Results reveal that stereotaxic injection of LV ‐mi R 124a in the DLS enhances ethanol‐induced CPP as well as voluntary alcohol consumption in a two‐bottle choice drinking paradigm. Moreover, mi R 124a‐silencer ( LV ‐si R 124a) as well as LV ‐ BDNF infusion in the DLS attenuates ethanol‐induced CPP as well as voluntary alcohol consumption. Importantly, LV ‐mi R 124a, LV ‐si R 124a and LV ‐ BDNF have no effect on saccharin and quinine intake. Our findings indicate that striatal mi R 124a and BDNF signaling have crucial roles in alcohol consumption and ethanol conditioned reward.