The Brain's Path to Addiction

Addiction is a complex disorder that affects the brain's reward circuit, beginning in the ventral tegmental area (VTA) above the brain stem. This area is home to dopamine neurons, whose axons extend to the nucleus accumbens. The striato-thalamo-orbitofrontal circuit is also involved in the compulsive impulse of substances, and is closely interconnected with other prefrontal and limbic regions, such as the anterior cingulate, insula, dorsolateral prefrontal cortex (DLPFC), and amygdala. The mesocortical dopaminergic pathway projects to the prefrontal cortex regions, including the orbitofrontal cortex (OFC) and anterior cingulate, while glutamate neurons project reciprocally between the PFC and amygdala, as well as from PFC to nucleus accumbens (NAc) and VTA.

This pathway has been implicated in obsessive-compulsive disorder (OCD), which shares common characteristics with addictive disorders such as lack of control over intrusive thoughts and compulsive behaviors that target substance procurement and administration. Advances in understanding the neurobiological basis of drug dependence have provided a scientific basis for treatment, prevention, and etiology of drug abuse. Drug dependence has long been associated with disturbances in the brain's reward systems. At the system level, neuronal circuits have been identified within the midbrain and forebrain connection of the medial forebrain bundle that mediate the acute reinforcing effects of drugs.

These circuits are composed of specific chemical neurotransmitters such as dopamine, endogenous opioid peptide systems, serotonin, GABA, and glutamate. These systems are modified during the development of dependency and remain sensitive to future shocks. Cellular studies have identified changes in function of different components of the mesencephalo-forebrain system that provide a framework for adaptive changes within neurons associated with withdrawal and sensitization. Neurotransmitter receptors and specific receptor subtypes are important for mediating these reinforcing actions, as well as providing a molecular basis for long-term plasticity associated with relapse and vulnerability.

Brain imaging can detect signs of addiction in the brain itself. Scans show that several different regions and pathways within the brain are affected by addiction, from an increase in neurotransmitters such as dopamine to reduced or increased activity in certain regions of the brain. Understanding how early adverse experiences can increase susceptibility to addiction is vital to formulating prevention and treatment plans. A cocktail of pharmacological interventions is needed for successful treatment of many addicted people.

Substance use disorders result from changes in the brain that can occur with repeated use of alcohol or drugs. Addiction is associated with changes in function of brain circuits involved in pleasure (the reward system), learning, stress, decision-making, and self-control. Tolerance and withdrawal occur when addicts try to stop using drugs or alcohol. We must adopt an attitude towards addictive diseases that offers extensive and intensive treatments. The addictive effects of major substances of abuse depend on dopaminergic activation of the mesolimbic pathway.

Researchers studying how addiction changes the brain have found clear markers of addiction within brain chemistry and structure. Pharmacological interventions guided by hypotheses of exhaustion or sensitization to addiction did not generate drugs useful for treating cocaine addiction. The powerful addictive effects of nicotine prove that “consciousness”, or taste for drug experience is not the most important effect of addictive drugs. There is a need for data on risks and outcome of opioid treatment for former addicts with pain, as well as patients with pain related to HIV infection.

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