Virus-delivered RNA interference in mouse brain to study addiction-related behaviors

The use of viral vectors for gene transfer to specific brain regions is a powerful tool for determining gene function in mouse behavioral models. We have employed a lentiviral vector to deliver small-hairpin RNAs to areas of mouse brain implicated in behaviors relevant to drug addiction, such as the nucleus accumbens and ventral tegmental area. Delivery of virus expressing small-hairpin RNAs results in sustained target gene knockdown by RNA interference. Mice can subsequently be tested for behavioral responses to various drugs of abuse over the course of several weeks or months. Here we describe a method for stereotaxic delivery of lentivirus to mouse brain. This method is widely applicable to any behavioral experiment in which the role of a specific gene in a particular brain region is to be elucidated.