Male and female mice with null mutation of the α5 nAChR subunit gene Chrna5 (α5 knockout) and their wildtype littermates were bred in our animal facilities. Brain structure and baseline behavioral measures between the knockout mice and wildtype littermates1. The mutant mice have been bred for more than 10 generations onto a C57BL6 background. Breeding was conducted by mating heterozygous pairs. All mice were housed in cages of 1–3 and were at least 6 weeks of age at the beginning of each experiment. Male Wistar rats weighing 275–300g were purchased from Charles River Laboratories and housed 1–2 per cage. Mice and rats were maintained in an environmentally controlled vivarium on a 12h:12h reversed light:dark cycle, and food and water were provided ad libitum until behavioral training commenced. During self-administration procedures, mice and rats were food restricted to 85–90% of their free-feeding body weight, but water was maintained without restriction. All procedures were conducted in strict accordance with the NIH Guide for the Care and Use of Laboratory Animals and were approved by the Institutional Animal Care and Use Committee of The Scripps Research Institute - Florida.