Addiction is a state characterized by compulsive engagement in rewarding stimuli, despite adverse consequences. The process of developing an addiction occurs through instrumental learning, which is otherwise known as operant conditioning.
Neuroscientists believe that drug addicts’ behavior is a direct correlation to some physiological change in their brain, caused by using drugs. This view believes there is a bodily function in the brain causing the addiction. This is brought on by a change in the brain caused by brain damage or adaptation from chronic drug use.[1][2]
In humans, addiction is diagnosed according to diagnostic models such as the Diagnostic and Statistical Manual of Mental Disorders, through observed behaviors. There has been significant advancement in understanding the structural changes that occur in parts of the brain involved in the reward pathway (mesolimbic system) that underlies addiction.[3] Most research has focused on two portions of the brain: the ventral tegmental area, (VTA) and the nucleus accumbens (NAc).[4]
The VTA is the portion of the mesolimbic system responsible for spreading dopamine to the whole system. The VTA is stimulated by ″rewarding experiences″. The release of dopamine by the VTA induces pleasure, thus reinforcing behaviors that lead to the reward.[5] Drugs of abuse increase the VTA's ability to project dopamine to the rest of the reward circuit.[6] These structural changes only last 7–10 days,[7] however, indicating that the VTA cannot be the only part of the brain that is affected by drug use, and changed during the development of addiction.
The nucleus accumbens (NAc) plays an essential part in the formation of addiction. Almost every drug with addictive potential induces the release of dopamine into the NAc.[8] In contrast to the VTA, the NAc shows long-term structural changes. Drugs of abuse weaken the connections within the NAc after habitual use,[9] as well as after use then withdrawal.[10]
Structural changes of learning
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Learning by experience occurs through modifications of the structural circuits of the brain. These circuits are composed of many neurons and their connections, called synapses, which occur between the axon of one neuron and the dendrite of another. A single neuron generally has many dendrites which are called dendritic branches, each of which can be synapsed by many axons.
Along dendritic branches there can be hundreds or even thousands of dendritic spines, structural protrusions that are sites of excitatory synapses. These spines increase the number of axons from which the dendrite can receive information. Dendritic spines are very plastic, meaning they can be formed and eliminated very quickly, in the order of a few hours.[citation needed] More spines grow on a dendrite when it is repetitively activated. Dendritic spine changes have been correlated with long-term potentiation (LTP) and long-term depression (LTD).[11][12]
LTP is the way that connections between neurons and synapses are strengthened. LTD is the process by which synapses are weakened. For LTP to occur, NMDA receptors on the dendritic spine send intracellular signals to increase the number of AMPA receptors on the post synaptic neuron. If a spine is stabilized by repeated activation, the spine becomes mushroom shaped and acquires many more AMPA receptors. This structural change, which is the basis of LTP, persists for months and may be an explanation for some of the long-term behavioral changes that are associated with learned behaviors including addiction to drugs.[13]
Research methodologies
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Animal models
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Animal models, especially rats and mice, are used for many types of biological research. The animal models of addiction are particularly useful because animals that are addicted to a substance show behaviors similar to human addicts. This implies that the structural changes that can be observed after the animal ingests a drug can be correlated with an animal's behavioral changes, as well as with similar changes occurring in humans.
Administration protocols
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Administration of drugs that are often abused can be done either by the experimenter (non-contingent), or by a self-administration (contingent) method. The latter usually involves the animal pressing a lever to receive a drug. Non-contingent models are generally used for convenience, being useful for examining the pharmacological and structural effects of the drugs. Contingent methods are more realistic because the animal controls when and how much of the drug it receives. This is generally considered a better method for studying the behaviors associated with addiction. Contingent administration of drugs has been shown to produce larger structural changes in certain parts of the brain, in comparison to non-contingent administration.[14]
Types of drugs
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All abused drugs directly or indirectly promote dopamine signaling in the mesolimbic dopamine neurons which project from the ventral tegmental area to the nucleus accumbens (NAc).[8] The types of drugs used in experimentation increase this dopamine release through different mechanisms.
Opiates
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Opiates are a class of sedative with the capacity for pain relief. Morphine is an opiate that is commonly used in animal testing of addiction. Opiates stimulate dopamine neurons in the brain indirectly by inhibiting GABA release from modulatory interneurons that synapse onto the dopamine neurons. GABA is an inhibitory neurotransmitter that decreases the probability that the target neuron will send a subsequent signal.
Stimulants
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Stimulants used regularly in neuroscience experimentation are cocaine and amphetamine. These drugs induce an increase in synaptic dopamine by inhibiting the reuptake of dopamine from the synaptic cleft, effectively increasing the amount of dopamine that reaches the target neuron.