Cocaine abuse remains a vexing public health problem that has been resistant to treatment. This grant has focused on understanding the changes in mood and behavior that occur within the binge abstinence pattern of cocaine use. This competing continuation will continue to improve our model of cocaine seeking and taking behavior and expand our focus upon the role of environmental stimuli in determining the effects of cocaine. First, we will determine how the motivation to take cocaine changes within a daily binge, across days of a binge, and after a period of cocaine abstinence. Participants will have the opportunity to smoke cocaine for several days in a row, but they will have to """"""""buy"""""""" each dose of cocaine using part of their daily earnings. How much they are willing to pay for cocaine will provide a measure of motivation. Second, we will examine the role of environmental stimuli in modulating the subjective and cardiovascular effects of smoked cocaine. Data obtained with laboratory animals demonstrate that the effects of stimulant drugs increase with experience, especially when drug administration occurs in the same environment. Because the laboratory is a novel environment for our research participants, we will be able to explore environmental influences on cocaine effects. Third, we will determine how environmental stimuli modulate an individual's motivation to smoke cocaine. We will train participants to associate one set of stimulus cues with 25 mg of smoked cocaine and a second set of cues with placebo smoked cocaine. We will then examine the motivational effects of these stimuli by presenting them paired with a low dose of cocaine, and then giving participants the opportunity to buy the low dose. Finally, we will investigate if the effects of cues paired with cocaine can be modulated by manipulation of dopamine (DA) receptor activity by determining the effects of the D1 antagonist ecopipam, and the nonselective DA agonist pergolide, on the response to the presentation of cues paired with cocaine. A better understanding of the variables affecting the duration and size of a cocaine binge and how periods of cocaine abstinence determine the timing of a binge, will be helpful in designing more effective behavioral and pharmacological interventions for cocaine abuse.
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