The development of genetically altered mice provides a novel way to examine the neurobiological mechanisms underlying both the reinforcing and addictive aspects of drugs of abuse. For example, mice in which the CB1 receptor has been altered can be used to assess the role of these receptors in the reinforcing effects of drugs of abuse. Although well-developed self-administration models exist for examining the reinforcing effects of drugs of abuse in rats, very few self-administration models have been developed for mice and those that do exist have not explored drug self-administration under an extensive range of conditions. Therefore, the current proposal has two goals. One of those goals is to develop drug self-administration procedures in mice that can be used to assess the consequences of prolonged drug exposure on the reinforcing effects of cocaine as well as the process of reinstatement (or relapse) following periods of drug deprivation. The second goal is to employ this set of procedures to assess the role of the CB1 receptor system in cocaine's reinforcing effects and relapse to cocaine seeking.