Title : Neurobiology of addiction
Abstract:
Addiction was historically viewed as a disease of “weak personality” and was not systematically addressed by the scientific and medical communities until the latter half of the 20th century. They are now commonly accepted as diseases of the brain caused by the impact of the drug on the brain (direct effects and neuroadaptations) modified by environmental factors.
Drug addiction can be considered a chronic brain disease that affects neurotransmission between neuronal circuits controlling behavior, emotion and cognition; characterized by excessive drug use, unsuccessful attempts in controlling drug intake leading to increase in anxiety and emotional pain. Thus, addiction results from repeated long-term exposure to drugs, leading to changes in central nervous system, especially in the midbrain dopamine system, resulting in an addictive state with complex behaviors such as dependence, tolerance, sensitization, and craving. However, addiction leading to loss of volitional control (opiates, nicotine and illicit use of psychostimulants), if left untreated, can cause major medical, social, and economic problems.
Drug addiction represents a dramatic dysregulation of motivational circuits caused by a combination of exaggerated incentive salience and habit formation, reward deficits and stress. Three phenomena characterize addiction: binge/intoxication, withdrawal/negative affect and craving (preoccupation/anticipation). Impulsivity and positive reinforcement often dominate the first stages, driving the motivation for drug seeking, and compulsivity and negative reinforcement dominate the terminal stages of the addiction cycle.
Binge/intoxication: Addictive substances and rewarding behaviors, increases the release of dopamine from mesolimbic projections to the nucleus accumbens. Thus, dopamine signals a pleasurable experience and is critical for the reinforcing effects which releases dopamine in the mesolimbic area, the corpus striatum, and the frontal cortex thereby promoting self-administration
Withdrawal/negative affect: The increase in negative emotional states in the withdrawal stage involve decrease in the dopamine function. These neuronal changes lead to dysphoric and stress-like responses. Repeated drug intake during withdrawal, results in a vicious cycle
Craving (preoccupation/anticipation): The craving and deficits in executive function in the so-called preoccupation/anticipation stage involve the dysregulation of key afferent projections from the prefrontal cortex to the basal ganglia and extended amygdala. Impaired dopamine and glutamate signaling in the prefrontal regions weakens the ability to resist strong urges to stop taking the drug. Thus, despite the potentially catastrophic consequences, it develops compulsive behavior and the associated inability to voluntarily reduce drug- taking behavior.
Molecular genetic studies have identified transduction and transcription factors that might mediate initial vulnerability, maintenance, and relapse associated with addiction
Summary:
- Addiction-relevant behaviors in animal studies model have led to an understanding of addiction neurobiology and identification of several genes mediating variation in drug preference and response
- The neurobiological pathways that modulate reward, stress resiliency and behavior inhibition are among those having underlying addiction liability.
- Variation in the neurobiology of addiction is genetically influenced by correlation of addiction liability with heritability.
- The individualization of treatment and prevention is likely to be advanced by the discovery of genetic predictors of the neurobiological pathways that underlie addiction
