Drug Cues, Conditioned Reinforcement, and Drug Seeking: The Sequelae of a Collaborative Venture With Athina Markou

Athina Markou spent a research period in my laboratory, then in the Department of Anatomy in Cambridge University, in 1991 to help us establish a cocaine-seeking procedure. Thus we embarked on developing a second-order schedule of intravenous cocaine reinforcement to investigate the neural basis of the pronounced effects of cocaine-associated conditioned stimuli on cocaine seeking. This brief review summarizes the fundamental aspects of cocaine seeking measured using this approach and the importance of the methodology in enabling us to define the neural mechanisms and circuitry underlying conditioned reinforcement and cocaine, heroin, and alcohol seeking. The shift over time and experience of control over drug seeking from a limbic cortical-ventral striatal circuit underlying goal-directed drug seeking to a dorsal striatal system mediating habitual drug seeking are also summarized. The theoretical implications of these data are discussed, thereby revealing the ways in which the outcomes of a collaboration can endure.