Which neurotransmitter system is primarily activated during the negative affect withdrawal phase of addiction?

The correct choice is corticotropic releasing factor (CRF) because this neurotransmitter plays a crucial role in the body’s stress response and is predominantly activated during the negative affect withdrawal phase of addiction. During this phase, individuals often experience heightened feelings of anxiety, depression, and stress, which are closely linked to an increase in CRF levels.

When a person is in withdrawal from a substance, the brain undergoes significant changes, particularly in the areas associated with stress and emotional regulation. CRF is released from the hypothalamus and stimulates the pituitary gland, leading to the release of adrenocorticotropic hormone (ACTH) and subsequently cortisol from the adrenal glands. This cascade of events exacerbates negative emotions and stress responses that are characteristic of withdrawal.

While other neurotransmitter systems such as endogenous opioids, dopamine, and serotonin are also involved in addiction and withdrawal, they are not primarily responsible for mediating the negative affect experienced during withdrawal. Endogenous opioids typically modulate feelings of pleasure and pain relief, while dopamine is more associated with the reward and reinforcement aspects of substance use. Serotonin's role in mood regulation cannot be overlooked, but it does not directly correlate to the specific stress and anxiety responses seen in the withdrawal phase