Many aspects of human behavior are guided by the reward system of the brain, which is also responsible for mood and motivation. The mood of an individual can affect his feeding, sexual activity and even cognitive processes. Neuropeptide systems in the brain play an important role in regulating mood and drugs of abuse can impact these systems. The dopaminergic system of the brain is a prime player in sensing reward. Kappa opioid receptors and dynorphins are part of the opioid peptide family and influence the brain reward system by modulating dopamine release in the striatum. Kappa-opioid receptor (KOPr) stimulation results in inhibition of dopamine release in the limbic cortical-striatopallidal circuit and can lead to a negative mood state. Drug addiction is a chronic relapsing disorder and addicts typically display a lack of motivation for natural rewards. Drugs of abuse stimulate dopamine release in the nigrostriatal and mesolimbic circuits with concomitant activation of a counter response by the KOPr/dynorphin system. With repeated drug exposure, neuroadaptations in the KOPr/dynorphin system have been found to occur and these can alter the functioning of the system resulting in relapse and neuropsychiatric co-morbidity in addiction. This article takes a look at the role of the kappa-opioid receptor and dynorphins in the brain reward system, the neurobiology of addiction and pharmacotherapeutic implications of the same.
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