Heroin is the most common illicit opioid drug and is deacetylated in the brain to morphine, which directly activates MOR, as does heroin. Endorphin and enkephalin peptides are the main neurotransmitters that mediate reward processes in the brain. It is the activation of the MOR, and subsequent meso-limbic opioid and dopamine signaling, which lends opioid drugs their addictive properties [48, 49]. Positive reinforcement therefore, drives early use as opioids are consumed for their pleasurable effects. As opioid use progresses to abuse and addiction, attempts to discontinue opioid use result in withdrawal and dysphoria. Negative reinforcement now motivates drug use, and drugs are taken to avoid the negative effects of withdrawal [49]. This cycle of positive and negative reinforcement causes both heroin and morphine to be highly addictive. Since morphine is also a commonly used analgesic, it is not surprising that other opioid analgesics targeting MOR also have high potentials for addiction. Although millions of people worldwide are dependent on heroin, addiction to prescription opioids also poses a significant public health problem. Increased use of opioids for pain management has led to a rapidly growing number of people addicted to these analgesics.
