Behavioral Neuroscience Research Branch
Neuropsychopharmacology Section
Overview
The Neuropsychopharmacology Section of the Behavioral Neuroscience Research Branch is devoted to research into brain mechanisms underlying the actions of addictive drugs, and into mechanism-based medication discovery and development for the treatment of addiction, craving, and relapse.
Areas of Research
- Evaluation of selective dopamine D3 receptor antagonists as potentially useful anti-addiction, anti-craving, and anti-relapse medications, using our preclinical screening algorithm.
- Evaluation of GAGAmimetic compounds as potentially useful anti-addiction, anti-craving, and anti-relapse medications, using our preclinical screening algorithm.
- Evaluation of slow-onset long-lasting dopamine transport inhibitors as potentially useful anti-addiction, anti-craving, and anti-relapse medications, using our preclinical screening algorithm.
- Evaluation of NAALADase inhibitors as potentially useful anti-addiction, anti-craving, and anti-relapse medications, using our preclinical screening algorithm.
- Study of brain mechanisms underlying addictive drug reward, addictive drug craving, and relapse to addictive drug-seeking behavior.
Future Directions
Our future direction will consist of follow-up and continuation of present lines of research, taking advantage of research breakthroughs and opportunistic advances in the field. Our lead GABAmimetic therapeutic compound, gamma-vinyl-GABA, has already advanced to clinical trials in human patients with promising initial open-label results. We have completed our evaluation of the initial lead compounds in our slow-onset long-acting dopamine transport inhibitor category, and we are now moving toward evaluation of follow-on compounds. Our lead dopamine D3 antagonist compound, SB277011A, has been discontinued at the human level due to unfavorable bioavailability and pharmacokinetic profiles in humans. However, our work with SB277011A in laboratory rodents over the last 5 years has been extraordinarily useful and productive, as it has clearly provided proof-of-concept of the potential clinical utility of dopamine D3 receptor antagonists as potential therapeutic agents for the treatment of addiction, craving, and relapse. Therefore, a substitute dopamine D3 antagonist lead compound has been identified, and preclinical trials with this new compound will commence in December 2005. Additional selective dopamine D3 receptor antagonists have been designed and synthesized in the Medicinal Chemistry Section, Medications Discovery Research Branch, NIDA/IRP, and these compounds will similarly be brought forward for full evaluation in out preclinical algorithm for identifying potentially useful anti-addiction, anti-craving, and anti-relapse medications. We will continue to follow up our discoveries that electrical or chemical stimulation of glutamatergic circuits originating in the hippocampus and basolateral amygdala triggers relapse to drug-seeking behavior, and our discovery that the basolateral amygdala mediates the effects of drug-associated environmental cues on brain-reward mechanisms.
Branch Chief: Eliot L. Gardner, Ph.D.
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Behavioral Neuroscience Research Branch
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