mechanisms of action drugs Flashcards
(35 cards)
A potentially addictive substance induces an increase in
dopaminergic transmission in the brain reward system
Explain the path of the primary reinforcing effect of a drug
release of dopamine from the ventral tegmental area (vta) to the nucleus accumbens (NAc).W
what is the vta?
The vta is a region extremely rich in DA (dopamine) neurons that resides in the midbrain
Where is the Nac located (nucleus accumbens)
the NAc is officialy part of the striatum, a big structure that resides in the forebrain, where it comprises the ventral part of it
What is the pathway called for dopamine that is responsible for reward?
mesolimbic pathway
Name all the pathways where dopamine plays an important role
- the mesolimbic pathway (reward)
- the mesocortical pathway ( decision making)
- the striatonigral pathway ( movement)
- tuberoinfundibular pathway (prolactine production)
What are natural drugs?
Natural drugs are substances extracted from plants, like cocaine and THC.The
natural ones are named the big five: cocaine, morphine, THC, alcohol and nicotine. Plants produce
these molecules (also named in many cases alkaloids) for protection.
What are synthetic drugs?
. Synthetic drugs are (mostly
illegally) elaborated in the lab starting from a natural compound or elaborated from scratch. An example
is LSD. Another example is MDMA, which should sound familiar if you have watched Breaking bad.
Name the big 5
big five: cocaine, morphine, THC, alcohol and nicotine
Explain the protection mechanism of the nicotiana tabacum plants
an example of protection is nicotine for nicotiana tabacum plants. At high dosage nicotine is
an efficient paralyzing agent. Nicotiana tabacum plants are very exposed to bugs that like chewing the
leaves of that plant leading it to die. To protect itself nicotiana tabacum produces nicotine when a bug
attacks its leaves. The bug will eat the leave together with a ridiculous high amount of nicotine in it.
Result? The bug will die paralyzed
Another drug classification is based on their effects, name them
stimulants (euphoria), depressants (sedation), hallucinogens (hallucinations), mixed
Name examples of hallucination, euphoria, sedation and mixed effect drugs
hallucination: LSD and Psilocybin
euphoria: amphetamine and cocaine
sedation: alcohol, ghb and heroin
mixed effect: thc and mdma
What drugs have the highest addictive potential?
Drugs that produce a strong enhancement in DA transmission (in particular in the VTA to NAc): this
effect produces intense to very intense reward when consumed (see rush/high).
What drugs have lower addictive potential?
Other drugs are able to induce just a little DA release from the VTA to the NAc. They mostly act on other
pathways, like for MDMA that works more on serotonin than DA. These drugs have lower addictive
potential.
Describe the difference in dopamine release between stimulants and depressants
Stimulants directly act on dopaminergic (VTA DA in this case) neurons, producing a direct
effect on DA transmission;
Depressants (and in some cases mixed drugs) produce an increase in VTA to NAc DA release
disinhibiting DA neurons (thus indirectly).
What is inhibitory and what is excitatory?
gaba is inhibitory and glutamate is excitatory
Describe what happens when dopamine is inhibited
In case of a strong activity of a substance (for instance) on one of these projecting neurons, the situation
can dramatically change. For instance, imagine the case of a drug that blocks GABA transmission to
VTA DA neurons. In this case there will
not be a balanced excitation/inhibition
anymore. There will be a lot of
glutamate and nearly zero GABA. The
result is a massive excitation of VTA
DA neurons and a consequent very
high release of DA to the NAc
Explain the indirect pathway on dopamine
This pathway is used for the depressants and the mixed drugs. Gaba is inhibited and this results into a stimulation of the vta dopamine in the NAc due to the difference in balance in gaba and glutamate
Explain the pathway of cocaine
It blocks the DAT (the dopamine transporter enzymes that care about the reuptake of excessive dopamine from the synaptic cleft). This will increase the availability of dopamine that can activate the dopaminergic receptors expressed on post-sysnaptic neurons
Explain the pathway of amphetamine
Also amphetamine blocks DAT (dopamine transport enzymes). So, an increase of dopamine transmission to the NAc and euphoria. On top of this, it also augments the packaging of dopamine in the presynaptic cleft. The packaging is done by VMAT (vesicular monoamine transporters). Amphetamine increases the activity of VMAT. so, an increase in the dopamine released and a decrease in the dopamine reuptake
Explain the Nicotine pathway
Nicotine is an agonist (versterker) at the level of the nicotinic acetylcholine receptors. In the brain, nAChRs are strongly expressed in the cortical regions and in the brain reward/limbic system. Hence, nicotine (activating these receptors)
exerts its functions as cognitive enhancing substance (in the cortex) and rewarding/addictive substance
(in the brain reward system). In the brain reward system nAChRs are massively expressed both on DA neurons from the VTA to the NAc and in their projecting neurons. AChRs are coupled with an ion-channel that,
when active, allows the influx of positive ions like sodium (Na+) and calcium (Ca2+). When nicotine
binds to these receptors it exerts an increase of positive ions in the dopaminergic axon terminals. This
effect excites the terminals, allowing a higher packaging of dopamine into vesicles (2) and release of
dopamine to the NAc (3). This produces the rewarding/reinforcing effects of nicotine.
What is the function of the nicotinic acetylcholine receptors?
These receptors are normally expressed in our brain to respond to the release of
acetylcholine (Ach), an important neurotransmitter involved in cognitive functions and movement. Ach
is also released in the periphery where it promotes the activity of both smooth and voluntary muscles. It
is, in fact, the molecule that allows our muscles to contract/relax, allowing movement.In the brain, nAChRs are strongly expressed in the cortical regions (that´s why Ach is involved in
cognitive functions) and in the brain reward/limbic system. Hence, nicotine (activating these receptors)
exerts its functions as cognitive enhancing substance (in the cortex) and rewarding/addictive substance
(in the brain reward system).
Explain the heroin pathway
It acts on receptors in the brain reward system, named mu-opioid receptors. These release endorphins. Activating these receptors will lead to suppressing the release of gaba to the vta da neurons. This results into hyper-excitation and an increase in the release of dopamine to the Nac. Mu-opiod receptors block the gaba release, because they belong to the gi-coupled receptors. which means when these receptors are activated (by endorphins or heroin) they induce metabolic changes in the cell that lead to suppress its activity. Result is that GABA neurons,
deactivated by MuR stimulation, do not release GABA until these MuR are still active.
What is heroin?
Heroin is a deacetylate form of morphine. Being deacetylate it gets much faster into the brain than
morphine. Both drugs (morphine and heroin) are opiates. They are thus classified as depressants as
once administered they cause sedation.
