Intranasal cocaine self-administration in male mice

Intravenous drug self-administration has been widely used in behavioral neuroscience to model addiction and heightened motivational states; however, the technique is notoriously difficult and its utility has been in steady decline. Here, circumventing prior issues, we established a procedure for intranasal drug self-administration in head-restrained male mice. This procedure does not require surgical expertise or indwelling implants, drives robust schedule- and dose-dependent responding, and results in high blood cocaine concentrations. In addition to improved ease of use and face validity for modeling cocaine use disorder, this work provides an example of volitional nasal drug insufflation by a non-human animal, a behavior canonically thought to be unique to humans across compounds.