Crosstalk Between Kappa Opioid and Dopamine Systems in Compulsive Behaviors

The strength of goal-oriented behaviors is regulated by midbrain dopamine neurons. Dysfunctions of dopaminergic circuits are observed in drug addiction and obsessive-compulsive disorder. Compulsive behavior is a feature that both disorders share, which is associated to a heightened dopamine neurotransmission. The activity of midbrain dopamine neurons is principally regulated by the homeostatic action of dopamine through D2 receptors (D2R) that decrease the firing of neurons as well as dopamine synthesis and release. Dopamine transmission is also regulated by heterologous neurotransmitter systems such as the kappa opioid system, among others. Much of our current knowledge of the kappa opioid system and its influence on dopamine transmission comes from preclinical animal models of brain diseases. In 1988, using cerebral microdialysis, it was shown that the acute activation of the Kappa Opioid Receptors (KOR) decreases synaptic levels of dopamine in the striatum. This inhibitory effect of KOR opposes to the facilitating influence of drugs of abuse on dopamine release, leading to the proposition of the use of KOR agonists as pharmacological therapy for compulsive drug intake. Surprisingly, 30 years later, KOR antagonists are instead proposed to treat drug addiction. What may have happened during these years that generated this drastic change of paradigm? The collected evidence suggested that the effect of KOR on synaptic dopamine levels is complex, depending on the frequency of K...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research