Intrathecal cocaine delivery enables long-access self-administration with binge-like behavior in mice

Abstract

Long-access intravenous drug self-administration shows diurnal alterations in drug intake, with escalation and binge patterns, in rats. A similar long-access model in mice would allow the use of genetically modified animals to better understand the molecular mechanisms underlying drug addiction and relapse. However, attempts to transfer this model to mice have been less successful, mainly because of technical difficulties with long-term maintenance of the indwelling catheter implanted into small veins. We devised an intrathecal probe implanted in the supracerebellar cistern as an alternative for intravenous drug administration to address this challenge and allow continuous, chronic drug self-administration in mice. We found that mice readily self-administered intrathecal infusions of cocaine as a drug reward, and, under daily 24-h access conditions, animals exhibited a binge-like behavior comparable to rats. This innovation enables a full analysis of long-access drug self-administration behavior in mice not possible with intravenous administration.