1999 — 2001 |
Fantegrossi, William E |
F31Activity Code Description: To provide predoctoral individuals with supervised research training in specified health and health-related areas leading toward the research degree (e.g., Ph.D.). |
Intravenous Self Administration of Mdma @ University of Michigan At Ann Arbor
Prior experiments have shown that primates (rhesus monkeys and baboons) will work for intravenous infusions of racemic MDMA at rates greater than or equal to those produced to obtain cocaine infusions. However, the reinforcing effects of the optical isomers of MDMA have not been previously assessed. Drug discrimination experiments suggest that the complex discriminative stimulus profile of racemic MDMA is attributable to the primarily dopaminergic stimulus effects of (+)-MDMA and the primarily serotonergic stimulus effects of (-)-MDMA. These differential effects of the stereoisomers on neurotransmitter systems have been confirmed in pharmacological studies. The objective of the proposed experiments is to further elucidate the differences between the optical isomers of MDMA by assessing their reinforcing effects in terms of (1) response rate under a fixed ratio schedule and (2) break point under a progressive ratio schedule. Additionally, self-administration data for racemic MDMA will be replicated in the fixed ratio study, and extended by means of a break point analysis in the progressive ratio study. In accord with previous self-administration studies, these behavioral endpoints will be compared with those produced by cocaine and saline, as well as methamphetamine (a drug with a more similar time course to MDMA) and LSD (a drug with more similar neurochemical effects to MDMA). Finally, the relationship between the rewarding and serotonin depleting effects of MDMA will be assessed by pharmacologically challenging self- administration behavior with pre-treatments of various neuroprotective agents.
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0.946 |
2006 — 2008 |
Fantegrossi, William E |
P51Activity Code Description: To support centers which include a multidisciplinary and multi-categorical core research program using primate animals and to maintain a large and varied primate colony which is available to affiliated, collaborative, and visiting investigators for basic and applied biomedical research and training. |
Behavioral Evaluation of Stimulant / Hallucinogen Drugs in Mice |
0.966 |
2006 — 2008 |
Fantegrossi, William E |
P51Activity Code Description: To support centers which include a multidisciplinary and multi-categorical core research program using primate animals and to maintain a large and varied primate colony which is available to affiliated, collaborative, and visiting investigators for basic and applied biomedical research and training. R21Activity Code Description: To encourage the development of new research activities in categorical program areas. (Support generally is restricted in level of support and in time.) |
Effects of Self-Administered Mdma On Brain and Behavior in Rhesus Monkeys
[unreadable] DESCRIPTION (provided by applicant): MDMA remains a .widespread drug of abuse worldwide, and may be peaking in recreational popularity. In recent years, use of MDMA has dramatically increased, perhaps due to the widespread perception that MDMA is "safer" than other drugs of abuse, such as cocaine and amphetamine. Despite the widespread recreational use of this drug, the reinforcing and neurochemical effects of MDMA have not been extensively characterized in laboratory animals, and the possibility that MDMA may produce enduring behavioral and neurochemical changes in rhesus monkeys as a consequence of chronic exposure in a self-administration paradigm has not been systematically investigated. The current body of evidence suggests that repeated, non-contingent, large doses of MDMA have the capacity to induce substantial decrements in various serotonergic markers in the primate, but the behavioral correlates of such changes are much more subtle and less well-described. The studies outlined in this proposal will utilize drug-naive rhesus monkeys to characterize the effects of acute MDMA on extracellular striatal monoamine concentrations via in vivo microdialysis in awake monkeys and compare them to those of the structurally similar psychostimulant amphetamine, correlate rates of acquisition and stability of MDMA self-administration with various pre-drug measures of monoamine function (ascertained via in vivo microdialysis, PET neuroimaging, and radioimmunoassay), track stability of MDMA-maintained responding over .an extended duration and assess the pharmacological specificity of observed behavioral decrements, and ascertain longitudinal changes in binding potential at dopamine and serotonin transporters associated with chronic MDMA self-administration via PET neuroimaging. Enduring changes in monoamine neurochemistry and hormonal responsiveness to serotonergic challenge associated with long-term MDMA self-administration will also be assessed via in vivo microdialysis and radioimmunoassay. Allowing animals to regulate their own drug intakes thus eliminates the need to rely on controversial models of allometric interspecies dose scaling and has previously resulted in MDMA intakes quite similar to those estimated in human users. Thus, these studies are likely to be more relevant to the potential human condition of MDMA-induced lasting neurochemical alterations and behavioral changes [unreadable] [unreadable]
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0.966 |