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Author Topic: Impacts of Drugs on Neurotransmission  (Read 1458 times)

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Impacts of Drugs on Neurotransmission
« on: June 13, 2019, 12:52:22 AM »

Opiod and opiate users will find an excellent paragraph on how different substances impact transmission and tolerance.

Impacts of Drugs on Neurotransmission

The defining features of drug intoxication and addiction can be traced to disruptions in neuron-to neuron signaling.

March 09, 2017 by Carl Sherman

Drugs can alter the way people think, feel, and behave by disrupting neurotransmission, the process of communication between neurons (nerve cells) in the brain. Many scientific studies conducted over decades have established that drug dependence and addiction are features of an organic brain disorder caused by drugs’ cumulative impacts on neurotransmission.

Scientists continue to build on this essential understanding with experiments to further elucidate the physiological factors that make a person prone to using drugs, as well as the full dimensions and progression of the disorder. The findings provide powerful leads for developing new medications and behavioral treatments.

This second article in our NIDA Notes Reference Series discusses the central importance of studying drugs’ effects on neurotransmission and describes some of the most common experimental methods used in this research. As with other articles in the series (see “Animal Experiments in Addiction Science”), we provide illustrative references from articles published in NIDA Notes.

What Is Neurotransmission ?

A person reads. The words on the page enter the brain through the eyes and are converted into information that is relayed, from one neuron to the next, to regions that process visual input and attach meaning and memory. When inside neurons, the information takes the form of an electrical signal. To cross the tiny gap, or synapse, that separates one neuron from the next, the information takes the form of a chemical signal. The specialized molecules that carry the signals across the synapses are called neurotransmitters.

The ebb and flow of neurotransmitters—neurotransmission—is thus an essential feature of the brain’s response to experience and the environment. To grasp the basic idea of neurotransmission, think of a computer. A computer consists of basic units, semiconductors, which are organized into circuits; it processes information by relaying an electric current from unit to unit; the amount of current and its route through the circuitry determine the final output. The brain’s corresponding basic units are the neurons—86 billion of them. The brain relays information from neuron to neuron using electricity and neurotransmitters; the volume of these signals and their routes through the organ determine what we perceive, think, feel, and do.

Of course, the brain, a living organ, is much more complex and capable than any machine. Neurons respond with greater versatility to more types of input than any semiconductor; they also can change, grow, and reconfigure their own circuits.

Getting the Message Across

The task in neurotransmission is to convey a signal from a sending neuron to a receiving neuron across an open space known as a synapse. All neurons accomplish this in approximately the same way.

The sending cell manufactures neurotransmitter molecules and stores them in packets called vesicles. When stimulated sufficiently, the neuron generates an electric signal and causes some vesicles to migrate to the neuron membrane, merge with it, open up, and release their contents into the synapse. Some of the released molecules drift across the synapse and link up, lock-and-key fashion, with molecules called receptors on the surface of the receiving neuron.

If the neurotransmitter is stimulatory (e.g., glutamate), its interaction with the receptor will raise the receiving neuron’s level of electrical activity and thereby increase the likelihood that it will, in turn, mobilize its vesicles and emit its own neurotransmitter. If the neurotransmitter is inhibitory (e.g., gamma-aminobutyric acid [GABA]), it will dampen the receiving neuron’s electrical activity and reduce its likelihood of releasing the neurotransmitter.

In this way, neurotransmitters relay information about the environment and our internal states from neuron to neuron through the brain’s circuits and, ultimately, shape how we respond. Neurotransmitters’ interactions with receptors can also set processes in motion that can alter the structure of receiving neurons, or raise (potentiate) or lower (depress) how strongly neurons respond when neurotransmitters link to their receptors in the future.

Once a neurotransmitter has interacted with its receptor on the receiving neuron, neuron to neuron communication is complete. The neurotransmitter molecules drop off the receptors. Loose again in the synapse, they meet one of three fates:

1. Some attach to another receptor.

2. Some encounter an enzyme, a chemical that breaks them apart.

3. Some reenter the sending neuron via a special structure that spans the neuron membrane, called a transporter. Once back inside the neuron, they are available for re-release in future neurotransmission episodes.

Normally, when drugs are not present, the cycle of release, breakup, and neuron re-entry maintains the amount of neurotransmitter in the synapse, and hence neurotransmission, within certain limits. In most cases, when an addictive drug enters the brain, it causes neurotransmission to increase or decrease dramatically beyond these limits.

The Basic Research Questions

Neuroscientists seeking to understand why people use drugs and the consequences of drug use focus on two issues:

1. Which neurotransmitter or neurotransmitters does the drug affect?

2. How does the drug alter neurotransmission?

Which Neurotransmitter or Neurotransmitters Does the Drug Affect ?

A person’s experiences when using a drug reflect the functional roles of the particular neurotransmitter(s) it disrupts. Each individual neuron manufactures one or more neurotransmitters: dopamine, glutamate, serotonin, acetylcholine, and/or any of dozens of others that scientists have identified to date. Each neurotransmitter is associated with particular effects depending on its distribution among the brain’s various functional areas (see Table 1).

Dopamine, for example, is highly concentrated in regions that regulate motivation and feelings of reward, and is a strong motivator for drug use. A neurotransmitter’s impact also depends on whether it stimulates or dampens activity of its target neurons.

Some drugs primarily affect one neurotransmitter or class of neurotransmitters. For example, prescription opioids and heroin produce effects that are similar to (but more pronounced than) those produced by the neurotransmitters endorphin and enkephalin: increased analgesia, decreased alertness, and slowed respiration.

Other drugs disrupt more than one type of neurotransmitter. Cocaine, for example, attaches to structures that regulate dopamine, leading to increases in dopamine activity and producing euphoria; it also produces changes in norepinephrine and glutamate systems that cause stimulant effects.

Because a neurotransmitter can stimulate or inhibit neurons that produce different neurotransmitters, a drug that disrupts one neurotransmitter can have secondary impacts on others. For example, nicotine stimulates cells directly by activating their receptors for acetylcholine, and indirectly by inducing higher levels of glutamate, a neurotransmitter that acts as an accelerator for neuron activity throughout the brain.

A key effect that all drugs that cause dependence and addiction appear to have in common—a dramatic increase in dopamine signaling in a brain area called the nucleus accumbens (NAc), leading to euphoria and a desire to repeat the experience—is in many cases an indirect one.

How Does the Drug Alter Neurotransmission?

Thumbnail image of the table.Neurotransmitters Implicated in Drug Use and Addiction
Click to view table.

As described above, neurotransmission is a cyclic process that transpires in several steps utilizing specialized components of the sending and receiving neurons. Identifying the precise step that a drug disrupts, and how, provides crucial insight into its impact on users, and is key to developing medical and behavioral interventions to inhibit, counter, or reverse the disruption.

Some drugs mimic neurotransmitters. Heroin and prescription opioids, for example, chemically resemble the brain’s natural opioids (endorphin and enkephalin) sufficiently to engage and stimulate their specialized receptors. Since heroin stimulates many more receptors more strongly than the natural opioids, the result is a massive amplification of opioid receptor activity. Marijuana mimics cannabinoid neurotransmitters, the most important of which is anandamide. Nicotine attaches to receptors for acetylcholine, the neurotransmitter for the cholinergic system.

Other drugs alter neurotransmission by interacting with molecular components of the sending and receiving process other than receptors. Cocaine, for example, attaches to the dopamine transporter, the molecular conduit that draws free-floating dopamine out of the synapse and back into the sending neuron. As long as cocaine occupies the transporter, dopamine cannot re-enter the neuron. It builds up in the synapse, stimulating receiving-neuron receptors more copiously and producing much greater dopamine impact on the receiving neurons than occurs naturally. The section “How Cocaine Motivates Drug Use and Causes Addiction” (below) enumerates some of cocaine’s interactions with the mechanisms of dopamine and other neurotransmitter signaling, and how they motivate use of the drug and contribute to dependence and addiction.

Finally, some drugs alter neurotransmission by means other than increasing or decreasing the quantity of receptors stimulated. Benzodiazepines, such as diazepam or lorazepam, produce relaxation by enhancing receiving neurons’ responses when the inhibitory neurotransmitter GABA attaches to their receptors.

What Changes Occur With Chronic Drug Use?

During the early phase of an individual’s drug experimentation, neurotransmission normalizes as intoxication wears off and the substance leaves the brain. Eventually, however, repeated drug use leads to changes in neuronal structure and function that cause long-lasting or permanent neurotransmission abnormalities. These alterations underlie drug tolerance (where higher doses of the drug are needed to produce the same effect), withdrawal, addiction, and other persistent consequences.

Some longer-term changes begin as adjustments to compensate for drug-induced increases in neurotransmitter signaling intensity. For example, the brain responds to repeated drug-induced massive dopamine surges in part by reducing its complement of dopamine receptors. This alleviates the drugs’ overstimulation of the dopamine system, but also contributes to features of drug dependence (e.g., susceptibility to drug withdrawal) and of addiction (e.g., compromised ability to respond to normal dopamine fluctuations produced by natural rewards). 

Similarly, methadone and some other opioids induce neurons to retract a portion of their mu opioid receptors, making them unavailable for further stimulation. The retraction is short-lived, after which the receptors return to the neuron surface, restoring normal responsiveness to subsequent stimulation. This dynamic of reducing and then restoring receptor availability may thwart the development of tolerance to these drugs. (Morphine, in contrast, does not cause receptors to retract, and the resulting opioid overstimulation triggers intracellular adjustments that appear to promote opioid tolerance.)

The drug-related mechanisms producing cumulative changes in neurotransmission sometimes are epigenetic in nature. While a drug cannot change a person’s genes, drugs can prod some genes to increase or decrease their production of proteins, leading to changes in neuron function or even actual reshaping of the physical structure of neurons. For example, in mice, cocaine alters important genetic transcription factors and the expression of hundreds of genes. Some of the resulting changes in the brain’s complement of proteins have been associated with increased drug-seeking and addiction-like behaviors in animals. Other changes, such as proliferation of new dendrites (branchlike structures on neurons that feature neurotransmitter receptors on their surface) may be compensatory.

Some epigenetic changes can be passed down to the next generation, and one study found that the offspring of rats exposed to THC—the main psychotropic component of marijuana—have alterations in glutamate and cannabinoid receptor formation that affects their responses to heroin.

Some drugs are toxic to neurons, and the effect accumulates with repeated exposures. For example, the club drug methylenedioxymethamphetamine (MDMA [Ecstasy/Molly]) damages axons (the branch of a neuron that releases its neurotransmitter into the synapse) that release serotonin; the result is disruption of serotonin neurotransmission that may underlie the memory problems that are sometimes experienced by heavy users.

Similarly, methamphetamine damage to dopamine-releasing neurons can cause significant defects in thinking and motor skills; with abstinence, dopamine function can partially recover, but the extent to which cognitive and motor capabilities can recover remains unclear.

this continues at the source link ...
« Last Edit: June 13, 2019, 04:20:23 AM by Chip »
I do not condone or support any illegal activities. All information is for theoretical discussion and wonder.
All activities discussed are considered fictional and hypothetical. Information of all discussion has been derived from online research and in the spirit of personal Freedom.


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