• Mechanisms of receptor sensitization and desensitization have been identified and are currently being related to mechanisms of addictive syndromes.

  • Use of positron-emission tomography and single photon emission computed tomography imaging to evaluate drug action on dynamics of energy utilization and neurotransmitter function in living animals and humans.

Nicotine
  • Characterization of the nicotinic-cholinergic receptor within the central nervous system.

  • Demonstration that nicotine reward may be mediated by dopamine release.

Opioids
  • Endogenous opioid receptors cloned and characterized (mu, kappa delta).

  • Mu, kappa, delta receptor locations mapped in the brain.

  • Regulation studies of opioid genes and processing of opioid peptides in normal and drug-treated states.

  • Receptor cloning increases the likelihood of developing more selective agonist and antagonist drugs for each receptor subtype.

  • Characterization of processes by which opioid receptor activation regulates neuronal function, secondary messenger systems, ion channel function, and gene expression.

Stimulants
  • Specific interaction sites for cocaine and amphetamine identified on dopamine transporter.

  • Genetically altered mice for dopamine receptors and transporter have produced exciting new models for role of dopamine in cocaine and amphetamine action and brain reward systems in general.

  • Excitatory amino acids implicated in dopamine-mediated effects of cocaine; potential therapeutic implications.



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