During abstinence, the short- and long-term sequelae of repeated dose (""""""""binge"""""""") cocaine use may have a substantial impact on the likelihood of relapse to cocaine use. The focus of this renewal is on the behavior and neurochemical changes of cocaine users during and after a smoked cocaine binge. Sex differences in subjective-effects, task performance, responsivity to drug-related cues, sleep, and neuroendocrine response to agonist challenges will be assessed for 2 weeks after binge cocaine use.
Aim 1. Examine prolactin (PRL) release following the administration of the serotonin (5HT) agonist dexfenfluramine in female cocaine users 2, 8, and 14 days after a cocaine binge during the follicular phase of the menstrual cycle. Hypothesis: The closer in time to the cocaine binge that dexfenfluramine is given, the smaller the increase in PRL levels.
Aim 2. Examine PRL release following the administration of the dopamine (DA) agonist bromocriptine in abstinent male and female cocaine users 2, 8, and 14 days after a cocaine binge. Hypothesis: The closer in time to the cocaine binge that bromocriptine is given, the smaller the decrease in PRL levels. We will compare the neuro-endocrine response to bromocriptine and dexfenfluramine in abstinent cocaine users to the responses observed in groups of non-drug users matched for age, sex, and menstrual cycle phase.
Aim 3. Examine responsivity to previously neutral stimuli, that have been paired with cocaine and placebo during training sessions, as a function of time since last cocaine use. Hypotheses: Stimuli paired with cocaine will elicit cocaine craving, alter mood, and disrupt cognitive task performance. Responsivity to stimuli will vary as a function of time since last cocaine use.
Aim 4. Examine the responses to smoked cocaine over the course of a 3-day binge of smoked cocaine use in female cocaine users, comparing the acute and residual effects of a cocaine binge during the follicular and mid-luteal phases of the menstrual cycle. Hypothesis: Within-session tolerance to the effects of cocaine will develop independently of menstrual cycle phase, but will not carry over from session to session within a day or between days. The proposed studies will provide data relevant to the behavioral and neurochemical mechanisms impacting the likelihood of relapse to cocaine use.
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