How Do Drugs Affect Synapses?
Drugs increase or decrease the effects of neurotransmitters. A drug that works against or blocks the effects of a neurotransmitter is defned as an antogonist. A drug that increases or pushes the effects is defined as an agonist. Some drugs can be both. This type of drug is called a mixed agonist-antagonist. This drug can be either depending on the dose. In other words it can be agonist at some doses and antagonist at other doses.
Drugs effect synaptic activities in quite a few ways. For a dopamine synapse, a drug can decrease or increase the sythesis of the neurotransmitter or even cause it to leak at its vesicles. It can increase its release, block its breaking down process, decrease its reuptake, inactivate chemicals, or even stimulate or stop the postsynaptic receptors.
Researchers say that a drug has an affinity for a specific type of receptor if it attaches or binds to that receptor. Some researchers have explained it sort of like a lock and a key.
Drugs differ in their affinity from strong to weak. The tendency to activate the receptor is the efficacy of a drug. For instance, a drug that binds to a receptor but does not stimulate it is said to be high in affinity but low in efficacy. This type of drug would be an antogonist because it occupies the receptor and prevents the effects of transmitting.
Drugs Effect Each Person Differently:
Each drug affects many kinds of synapses. Antipsychotic drugs block, for the most part, dopamine receptors but have some effect on other types of receptors as well. For each neurotransmitter, the brain has different types of receptors, which aslo differ in behavioral functions. People differ in their amounts of each type of receptor. Some people have genes that change the shape and effectiveness of certain receptors. What this means is one person might have a large number of dopamine type D4 receptors and very few D1 or D2 receptors, where someone else has more D1, less D4, and a normal amount of D2 receptors. A drug that alters dopamine synapses can have different effects on different people.
Researchers in 1954 found that brain stimulation is reinforcing and almost completely and exclusively in tracts of axons that release dopamine. Dopamine has been known as a pleasure chemical. Addictive drugs have a very large ability to be over-bearing on the user's cravings.
Many extremely highly addictive drugs are stimulant drugs. These drugs produce alertness, mood elevation, excitement, lower fatigue, and usually give an increased motor activity. Each of these drugs increase the activity of the dopamine receptors.
Amphetamine produces dopamine synapses stimulation by increasing the release of dopamine from the presynaptic terminal. The presynaptic terminal usually reabsorbs released dopamine via a protein called the dopamine transporter. Amphetamine reverses the transporter, forcing the cell to excrete dopamine instead of absorbing it. Cocaine stops the reuptake of dopamine, serotonin, and norepinephrine, which lengthens the effects.
Research shows that the behavioral effects of cocaine are dependent on the increasing dopamine effects and also on serotonin effects. Since both Cocaine and damphetamine raise dopamine activity, their behavorial effects are quite similar.
The effects of amphetamine and Cocaine are intense but doesn't last long. By increasing the release of domapine or lowering its reuptake the drugs increase the buildup of dopamine in the synaptic cleft. However, the extra dopamine washes away from the synapse quicker than the presynaptic cell can synthesize more dopamine. Also the excess dopamine activates autoreceptors on the presynaptic terminal, giving a negative signal, which reduces further release of dopamine. The end result is that within a few hours of cocaine or amphetamine the user will fall into a depressed state that is well-known as "crashing".
Tolerance by the user also plays a role in the effects of the drug. After someone has used a drug repeatedly, the drug will release less dopamine and more of the transmitter called dynophin, wich counteracts the effects of the drug. This will result in increasing the frequency and dosage of the drug
Long term use of these types of drugs can cause long-term, permanent disruption of brain functions. Long-term cocaine use causes lasting changes in blood flow and metabolism in the brain, which greatly increases their chances of epilepsy, stroke, and memory functions.
Giros, Jaber, Jones, Wight-man`, & Caron, 1996
Rocha et al., 1998; Volkow, Wang, Fischman, et al., 1997
R.A. Harris, Brodie, & Dunwiddie, 1992; wise & Bozarth, 1987
Xu, Hu, cooper, White, & Tonegawa, 1996
London et al., 1990
Mattay et al., 1996
Gainetdinov et al., 1999\
McCann, Lowe, & Ricaurte, 1997
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