Addiction is a state characterized by compulsive involvement in useful stimuli, despite adverse consequences. The process of developing an addiction occurs through instrumental learning, also known as operant conditioning.
Neuroscientists believe that the behavior of drug addicts is a direct correlation with some physiological changes in their brains, caused by the use of drugs. This view believes there is a body function in the brain that causes addiction. This is caused by changes in the brain caused by brain damage or adaptation of chronic drug use.
In humans, addiction is diagnosed according to a diagnostic model such as Diagnostic and Statistical Manual of Mental Disorder, through observed behavior. There have been significant advances in understanding the structural changes occurring in parts of the brain involved in the underlying gift path (mesolimbic system) that addiction. Most studies focus on two parts of the brain: ventral tegmental area (VTA) and nucleus accumbens (NAc).
The VTA is part of the mesolimbic system that is responsible for propagating dopamine throughout the system. VTA is stimulated by "valuable experience". The release of dopamine by VTA induces pleasure, thus reinforcing the behavior that leads to rewards. Drug abuse increases the ability of the VTA to project dopamine to the rest of the prize circuit. This structural change lasts only 7-10 days, however, indicating that the VTA can not be the only part of the brain that is affected by drug use, and changes during the development of addiction.
Nucleus accumbens (NAc) play an important part in the formation of addiction. Virtually every drug with an addictive potency induces the release of dopamine into the NAc. Unlike the VTA, NAc shows long-term structural changes. Drug abuse weakens the connections inside the NAC after daily use, as well as after use then withdrawal.
Video Addiction-related structural neuroplasticity
Perubahan struktur pembelajaran
Learning through experience occurs through modification of the brain's structural circuitry. This circuit consists of many neurons and connections, called synapses, which occur between the axons of one neuron and the other dendrites. A single neuron generally has many dendrites called dendritic branches, each of which can be synergized by many axons.
Throughout the dendritic branches there are hundreds or even thousands of dendritic spines, structural bulges that are the site of excitatory synapses. These spikes increase the number of axons from which dendrites can receive information. Dendritic spines are very plastic, which means they can be formed and removed very quickly, in a sequence of several hours. More thorns grow on dendrites when activated repeatedly. Dendritic spine changes have been correlated with long-term potentiation (LTP) and long-term depression (LTD).
LTP is a way of connecting between neurons and synapses reinforced. LTD is the process by which synapses are attenuated. In order for LTP to occur, NMDA receptors on dendritic spine transmit intracellular signals to increase the number of AMPA receptors in post-synaptic neurons. If the spine is stabilized by repeated activation, the spine becomes mushroom-shaped and acquires many AMPA receptors. This structural change, which is the basis of LTP, lasts for months and can be an explanation for some of the long-term behavioral changes associated with learned behaviors, including addiction.
Maps Addiction-related structural neuroplasticity
Research methodology
Animal model
Animal models, especially rats and mice, are used for many types of biological research. An addicted animal model is useful because animals that are addicted to a substance exhibit similar behaviors to a human addict. This implies that structural changes that can be observed after animals ingest drugs can be correlated with changes in animal behavior, as well as with similar changes that occur in humans.
Administrative protocol
Drug administration often abused may be conducted either by experimentation (non-contingent), or by self-administration method (contingent). The latter usually involves the animal pressing the lever to receive the medicine. Non-contingent models are generally used for comfort, which is useful for examining the pharmacological and structural effects of drugs. Contingent methods are more realistic because animals control when and how much medicine they receive. This is generally considered a better method for studying addiction-related behaviors. Continuous administration of drugs has been shown to result in larger structural changes in certain parts of the brain, compared with non-contingent administration.
Drug type
All drugs that are misused directly or indirectly promote dopamine signaling in dopamine mesolimbic neurons projected from the ventral tegmental area to nucleus accumbens (NAc). The types of drugs used in the experiment increase the release of this dopamine through different mechanisms.
Opiat
Opiates are a class of sedatives with the capacity to relieve pain. Morphine is an addiction commonly used in animal addiction testing. Opiates stimulate dopamine neurons in the brain indirectly by inhibiting GABA release from the modulatory interneuron that synapses to dopamine neurons. GABA is a neurotransmitter resistor that lowers the probability that the target neuron will send the next signal.
Stimulants
The stimulants used regularly in neuroscience experiments are cocaine and amphetamines. These drugs induce increased synaptic dopamine by inhibiting the reuptake of dopamine from the synaptic cleft, effectively increasing the amount of dopamine reaching the target neuron.
Gift path
The reward path, also called the mesolimbic system of the brain, is part of the brain that records gifts and pleasures. This circuit reinforces behaviors that lead to positive and fun outcomes. In drug addiction, drug-seeking behaviors are reinforced by dopamine invasion that follows the administration of drug abuse. The effects of drug abuse in the ventral tegmental area (VTA) and nucleus accumbens (NAc) have been studied extensively.
Drug abuse changes the complexity of dendritic branching as well as the number and size of branches in both VTA and NAc. [7] With this correlation, these structural changes have been linked to addictive behaviors. The effect of structural changes on these behaviors is uncertain and research has yielded conflicting results. Two studies have shown that increased dendritic spine density due to cocaine exposure facilitates sensitization of behavior, while two other studies produce conflicting evidence.
In response to drug abuse, structural changes can be observed in the size of neurons and the shape and number of synapses in between. The nature of structural changes specific to the type of drug used in the experiment. Opiates and stimulants produce the opposite effect in structural plasticity in the reward pathway. It is not expected that these drugs will cause the opposite structural changes in the brain because both classes of drugs, opiates and stimulants, both cause similar behavioral phenotypes.
Both of these drugs induce acute locomotor activity increase, chronic self-administration improvement, and dysphoria when the drug is taken. Despite its effect on opposite structural plasticity, there are two possible explanations for why this drug still produces the same addictive indicator: Either this change produces the same behavioral phenotype when any change from the baseline is generated, or important changes that lead to addictive behavior can not be measured by measuring bone density back dendritic.
Opiates decrease spinal density and dendritic complexity in nucleus accumbens (NAc). Morphine decreases bone density regardless of treatment paradigm. Either a chronic or intermittent morphine will produce the same effect. The only case in which opiates increase dendritic density is by exposure to chronic morphine, which increases spinal density in pyramidal neurons in the orbitofrontal cortex. Stimulants increase spinal density and dendritic complexity in nucleus accumbens (NAc), ventral ventral areas (VTAs), and other structures in reward circuits.
ventral tegmental area
There are neurons with cell bodies in the VTA that release dopamine to certain parts of the brain, including many of the limbic regions such as NAc, medial prefrontal cortex (mPFC), dorsal striatum, amygdala, and hippocampus. The VTA has dopaminergic neurons and GABAergic which both project to NAc and mPFC. GABAergic neurons in the VTA are also synced on local dopamine cells. In the non-drug model, VTA dopamine neurons are stimulated by a rewarding experience. The release of dopamine from VTA neurons appears to be the driving action behind drug-induced pleasure and rewards.
This effect induces LTP in a 24 hour VTA cut after exposure to drugs has been shown to use morphine, nicotine, ethanol, cocaine, and amphetamine. These drugs have little in common except that they are all potentially addictive. This is evidence supporting the relationship between structural changes in VTA and the development of addiction.
Changes other than LTP have been observed in the VTA after treatment with substance abuse. For example, the size of the neuronal body decreases in response to opiates.
Although structural changes in VTAs demanded by exposure to addictive drugs generally disappear after one or two weeks, the target area of ​​the VTA, including NAc, may be where long-term changes associated with addiction occur during the development of addiction.
Nucleus accumbens
Nucleus accumbens play an integral role in addiction. Almost every addictive drug abuse induces the release of dopamine to the nucleus accumbens. NAc is essential for instrumental learning, including the recovery of cue-induced drug-seeking behavior. It is also involved in mediating the initial strengthening effect of addictive drugs. The most common type of cell in the NAc is the GABAergic medium spiked neuron. These neurons project an inhibitory connection to the VTA and receive excitatory input from various other structures in the limbic system. The change in synaptic input of excitatory into these neurons has been shown to be important in mediating addictive behavior. It has been shown that LTP and LTD occur in NAC synapses excitatory.
Unlike the VTA, a single dose of cocaine does not cause a change in the potentiality of the NAc excitatory synapses. LTD was observed in intermediate spiny neurons in NAc after two different protocols: daily cocaine administration for five days or a single dose followed by 10-14 days of withdrawal. This suggests that structural changes in NAc are associated with long-term behavior (rather than acute responses) associated with addiction such as drug seeking.
Human relevance
Relapse
Neurologists who study addiction define relapse as a recovery of drug-seeking behavior after a period of abstinence. The structural changes in the VTA are hypothesized to contribute to recurrence. Once the molecular mechanism of relapse is better understood, pharmacological treatment can be developed to prevent it.
Relapse is the biggest problem for recovering addicts; an addict may be forced not to use drugs when they are treated at a nursing home, but once they leave the clinic they risk a relapse. Relapse can be triggered by stress, cues related to past drug use, or re-exposure to the substance. The animal model of relapse can be triggered in the same way.
Find drugs for addiction
The goal of addiction research is to find ways to prevent and reverse the effects of addiction on the brain. Theoretically, if structural changes in the brain associated with addiction can be blocked, then the negative behavior associated with the disease will never develop.
Structural changes associated with addiction can be inhibited by NMDA receptor antagonists that block NMDA receptor activity. NMDA receptors are essential in LTP and LTD processes. These class medicines are unlikely candidates for the prevention of pharmacological addictions because these drugs are themselves used in recreation. Examples of NMDAR antagonists are ketamine, dextromethorphan (DXM), phencyclidine (PCP).
References
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