The objective of this contract is to determine the in vivo efficacy of novel compounds in animal models of relapse using cocaine, nicotine, methamphetamine, or opioids. This includes the following tests in animals trained to self- administer cocaine (for example): (1) the ability of a test compound to block footshock or other stressor-induced reinstatement of responding after a period of experimental extinction; (2) the ability of a test compound to block or reduce priming-induced reinstatement of responding after a period of extinction; and (3) the ability of a test compound to block the effects of a conditioned cue (previously paired with the training drug) to reinstate responding for the training drug after a period of extinction.