Which neurotransmitter is most affected by withdrawal from heroin?

The neurotransmitter that is most affected by withdrawal from heroin is norepinephrine. Heroin is an opioid that primarily acts on the body's opioid receptors, leading to a significant increase in dopamine levels in the brain, which is associated with its pleasurable effects. However, during withdrawal from heroin, the acute effects of opioid use diminish, and the body experiences a rebound effect, particularly involving norepinephrine.

When heroin is used, it inhibits the release of norepinephrine, resulting in lower baseline levels in the body. Upon withdrawal, as opioid receptors no longer receive stimulation from heroin, there is a compensatory increase in the release of norepinephrine. This surge contributes to many withdrawal symptoms such as increased heart rate, anxiety, sweating, and restlessness. These effects are often described as part of the physiological stress response, which is tied closely to norepinephrine's role in the body's fight-or-flight mechanism.

Therefore, the role of norepinephrine in the withdrawal process is critical, as it helps to explain the range of symptoms experienced during opioid withdrawal, distinct from the initial euphoric effects associated with dopamine release.