Kappa opioids as potential treatments for stimulant dependence

Stimulant abuse is a major problem in the United States and the development of pharmacological treatments for stimulant abuse remains an important therapeutic goal. Classically, the "dopamine hypothesis" has been used to explain the development of addiction and dependence of stimulants. This hypothesis involves the direct increase of dopamine as the major factor in mediating the abuse effects. Therefore, most treatments have focused on directly influencing the dopamine system. Another approach, which has been explored for potential treatments of stimulant abuse, is the use of kappa opioid agonists. The kappa receptor is known to be involved, via indirect effects, in synaptic dopamine levels. This review covers several classes of kappa opioid ligands that have been explored for this purpose.