PP Final 2

• Down-regulation: number of receptors decrease in response to rising nt levels, reducing cellular activity
• Early attempts to explain drug addiction phenomena was by Physical-Dependence, which later failed to explain some aspects of addiction leading to emergence of Positive-Incentive theory
• Physical Dependence theory of addiction suggests that individuals who develop physical dependence on drugs are driven to self-administer the substance to decrease withdrawal symptoms.
• Addicts are caught in a cycle of drug taking and withdrawal, forming a pattern that is difficult to break.
• Early drug treatment programs were designed to break this cycle by gradually withdrawing drugs in a hospital setting, aiming to address physical dependence.
• The theory faced criticism as almost all detoxified addicts, after being released from the hospital, tended to return to drug use, suggesting that physical dependence alone might not explain addiction.
• Evidence contradicting physical-dependence theory include that some highly addictive drugs produce little withdrawal distress (e.g., cocaine), challenging the idea that withdrawal symptoms are the primary driving force behind continued drug use; the pattern of drug taking often involves self-imposed cycles of binges and detoxification, indicating a more complex behavioral aspect beyond physical dependence.
• Detoxified addicts: addicts who have no drugs in their bodies and no longer experience withdrawal symptoms
• Positive-incentive theory: drugs are often taken not just to avoid withdrawal symptoms but more frequently due to the motivation by the anticipated pleasurable consequences they provide, hence it emphasizes the seeking of rewards rather than the avoidance of aversive aftereffects.
• Positive-incentive theory led investigators exploring the physiological bases of addiction to focus on the neural systems in the brain associated with pleasure and reward in addiction which is the mesotelencephalic dopamine system.
• Neurons from the VTA (ventral tegmental area) project to the limbic system and cortex, forming the mesocortical limbic pathway. The mesotelencephalic dopamine system, particularly the pathway from VTA to the nucleus accumbens (NAc), is involved in self-stimulation and reinforcement. NAc, part of the striatum in the basal ganglia, serves as a key region at the intersection of the limbic system (emotion control) and the striatum (movement control). 
• Dopamine is identified as the neurotransmitter in the brain reward circuit activated by abused drugs.
• Despite the varied actions of abused drugs in the brain, they share a common property – the regulation of the brain reward pathway extending from VTA to NAc. While both cocaine and opioids are reinforcing, opioids are sedating, and cocaine is a powerful stimulant, illustrating the diversity in drug effects despite a common impact on the reward pathway
• People report taking drugs to gain pleasure, to produce alterations in consciousness, to conform to the behavior of their peers, and to relieve stress and other negative emotions. 
• The process of an individual becoming an addict starts with regular and sustained drug use at adequate doses and frequencies.
• Chronic drug use induces long-lived changes in brain functioning, representing compensatory adaptations to the drug's impact.
• The brain undergoes adaptations to maintain balance (homeostasis) in response to continuous drug exposure.
• Long-term potentiation changes occur in brain regions like the NAc and VTA.
• Stimulation of neurons leads to increased dopamine release in the NAc, reinforcing drug-seeking behavior.
• Drug-seeking behavior can be triggered by stressful situations, as drugs provide temporary relief from difficulties.
• The combination of altered brain circuitry, reinforced drug-seeking behavior, and coping mechanisms can lead to addiction in some individuals.