Addictions focus on alterations in the brain's mesolimbic dopamine pathway, also known as the reward circuit, which begins in the ventral tegmental area (VTA) above the brain stem. The cell bodies of dopamine neurons arise in the VTA and their axons extend to the nucleus accumbens. The pathway involved in the compulsive impulse of substances is the striato-thalamo-orbitofrontal circuit. This circuit is closely interconnected with other prefrontal and limbic regions, including the anterior cingulate, the insula, the dorsolateral prefrontal cortex (DLPFC) and the amygdala.
Innervation includes both the mesocortical dopaminergic pathway, which projects to the PFC regions that include the OFC and the anterior cingulate11, and glutamate neurons that project reciprocally between the PFC and the amygdala, as well as from PFC to NAc and VTA, 96 has been implicated in obsolessive compulsive disorder (TOC), a syndrome that shares common characteristics with addictive disorders; i.e., the drive for drugs and alcohol includes lack of control over intrusive thoughts and compulsive behaviors that target substance procurement and administration, 106 107.Significant advances in understanding the neurobiological basis of drug dependence over the past 25 years are beginning to provide a solid scientific basis for the treatment, prevention and etiology of drug abuse. Drug dependence has long been associated with some disturbance of the brain's reward systems. At the system level, specific neuronal circuits have been identified within the midbrain and forebrain connection of the medial forebrain bundle that mediate the acute reinforcing effects of drugs (Figure 3, (Koob, 1992a). These neuronal circuits are composed of specific chemical neurotransmitters and include midbrain dopamine systems, endogenous opioid peptide systems, and other neurotransmitters such as serotonin, GABA and glutamate.
These systems appear to be modified during the development of dependency and appear to remain sensitive to future shocks. Cellular studies have identified specific changes in the function of different components of that mesencephalo-forebrain system and are beginning to provide a framework for adaptive changes within neurons that are associated with withdrawal and sensitization (Nestler, 1999). neurotransmitter receptors and specific receptor subtypes important for mediating these reinforcing actions, but they have also begun to provide a molecular basis for long-term plasticity associated with relapse and vulnerability (Nestler, 199). The rest of this section highlights some of the neurobiological advances resulting from research on individual differences; reinforcing neural substrates, withdrawal, tolerance and relapse; pharmacotherapy and brain imaging.
Substance use disorders result from changes in the brain that can occur with repeated use of alcohol or drugs. The most serious expression of the disorder, addiction, is associated with changes in the function of brain circuits involved in pleasure (the reward system), learning, stress, decision-making and self-control. These scans show us 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, addiction has a direct impact on the structure, functioning and health of the brain.
Experience with other chronic medical and psychiatric disorders, such as depression, epilepsy, hypertension and schizophrenia, suggests that a cocktail of pharmacological interventions will be needed for the successful treatment of many addicted people. Many addictive drugs, such as alcohol, produce tolerance and addicts experience withdrawal when they try to stop using them. Although addiction can manifest itself in many different ways, from physical changes to behavioral responses, brain imaging and scans can also detect signs of addiction in the brain itself. Understanding the mechanisms by which early adverse experiences can increase susceptibility to addiction is vital to properly formulate prevention and treatment plans.
We must adopt the same attitude towards addictive diseases and offer extensive and intensive treatments. Therefore, a general assumption that has guided addiction research for much of the past two decades has been that the addictive effects of the major substances of abuse depended 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 AD did not generate drugs useful for the treatment of cocaine addiction.
The relative absence of inhibitory restraint in addicted subjects is observed in standardized and experimental neurocognitive measures of impulsivity and decision-making 137142, which reveal deficits in the ability of addicted subjects both to inhibit prepotent (or strongly habituated) responses137 and to choose greater rewards. delayed rather than less immediate rewards. Although some preliminary studies have explored the effect of parenting interventions on parents with addiction problems (5), little is known about the direct role of parents in preventing later addiction problems in their children (5). The powerful addictive effects of nicotine prove that “consciousness”, the taste for the experience of drugs is not the most important effect of addictive drugs.
There is a particular need for data on the risks and outcome of opioid treatment of former addicts with pain, as well as patients with pain related to human immunodeficiency virus (HIV) infection. . .