• Mechanisms of somatic dependence established (locus coeruleus and other brainstem nuclei); predicted use of clonidine or other alpha-adrenergic drugs for treatment of somatic withdrawal.

Nicotine
  • Development of a model wherein animals self-administer nicotine to blood levels approximating those of human cigarette smokers.

  • Models for examination of "inhaled" nicotine.

Opioids
  • Discovery of mechanisms by which opioids activate brain reward pathways (via VTA and NAc).

  • Modulation of brain reward pathways by kappa agonists and antagonists; potential role of kappa agonists in blocking opioid reinforcement.

  • Prevention and/or reversal of opioid tolerance and dependence by NMDA antagonists, CCK antagonists, delta receptor agonists, and nitric oxide synthase inhibitors.

  • Substantial progress on molecular adaptations produced by acute or chronic opioids in the brain.

Stimulants
  • Development of robust animal models of cocaine and amphetamine self-administration.

  • Experimental evaluation of selective dopamine-subtype-selective agonists, antagonists, partial agonists, and other therapies as treatments for cocaine dependence.

  • Demonstration that the neurochemical consequences of cocaine self-administration are different from involuntary injection of cocaine, suggesting different transmitter pathways involved in anticipation of reward versus behavioral response.

Alcohol
  • Development of several genetically stable strains of high- or low-alcohol-preferring rats from common outbred animal stock.



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