Addiction Flashcards
Psychostimulants
The most common known psychostimulants are…
All act by binding to…
These drugs all directly enhance the extracellular levels of…
This can occur through two different mechanisms: either by blocking the transporter and thus prohibiting the reuptake of dopamine into the presynaptic terminal, or by reversing the transporter which also leads to an increase in dopamine release….
amphetamine, methamphetamine, cocaine, and MDMA.
dopamine, noradrenaline and serotonin transporters
dopamine by influencing the dopamine transporter.
not in cocaine
MDMA is an active ingredient of…
Stimulates social behavior, less addictive than amphetamine and cocaine
ecstasy, is structurally related to (meth)amphetamine and also increases vigilance and motor activity.
Opiates and opioids are substances that are structurally and functionally related to…
The opioids include…
Opiates and opioids act as…
morphine
fentanyl, heroine and methadone
direct agonist of the μ-opioid receptor.
Opioids and Opiates increase the extracellular concentration of dopamine.
Inhibitory effect of μ-opioid receptors on the release of GABA in the VTA. This leads to a disinhibition of the dopaminergic cells and hence an increased release in the nucleus accumbens.
Opiates are located on the GABAergic interneurons on the pre-synaptic terminal
µ-opioids reduce (when stimulated) the release of GABA
GABA is a inhibitory NT, under normal circumstances interacts with GABAa receptor (ionotropic receptor)
Disinhibit the cells, reduce the inhibition of the dopaminergic cells, cells fire more actively, more dopamine is released at terminal region and more dopamine can interact with the GABAergic cells
Increase in dopamine in the extracellular space in the nuc acc
Opioids - increase the firing rate of the dopaminergic cells by removing the break that is induced by GABA
Cannabinoids
- Many different components
- Most important THC (tetrahydrocannabinol)
- Have many medicinal properties (pain relief, anticonvulsant, etc)
- Cannabinoids act as agonists of the…
- CB1 receptors relevant for…
- CB1 and CB2 receptors are stimulated by…
- These endocannabinoids are highly…
- These endocannabinoids are…
CB1 and CB2
addictive properties
endogenous cannabinoids anandamide and 2-arachidonoylglycerol
lipophilic substance, and can therefore not be stored in presynaptic vesicles like other NT
synthesized on demand, when the cells are stimulated. CB1 receptors are located presynaptically and act by inhibiting the release of other NT.
NT is released in the post-synaptic cell, activates an enzyme
2 AG and AEA are…
Because the drugs are lipophilic….
These receptors are located…
µ-opioids are located on the…
Cannabinoids such as THC is taken, it stimulates the CB1 receptors that leads to a…
Takeaway the break of the dopaminergic cell and therefore, increase the firing of dopamine and increase the dopamine extracellularly in the nuc acc.
synthesized and interact with CB1 receptor
can easily penetrate through cell membrane and directly interact with the receptor
pre-synaptically
GABAergic interneuron
reduced release of GABA.
Alcohol
- Active ingredient ethanol
- Most harmful of all addictive substances
- Acts on multiple receptors
- Has multiple, dose dependent effects (low dose excitatory, high dose more sedative)
- ethanol has a very complex and…
- PAM for GABAA receptor
- Non-competitive antagonist for glutamate receptors
to a large degree unknown pharmacology
Drugs of abuse – Acute effect
when an individual takes a drug of abuse for the first time, they generally feel a strong…
This then plateaus for some time, and as the drug wears off (is metabolized) it generally leads to a phase of…
euphoria (positive feeling).
dysphoria (negative feeling).
Drugs of abuse – Rat Studies
Rat placed in operant chamber with two levers
Infusion pump – injection of drug
Rat needs to put in more effort to get the drug
Rapidly increase release of…
When dopamine returns back to normal it undershoots, the dopamine does not immediately…
Aversive low effect immediately following the initial high
Have initial high induced by increase of dopamine release, goes below baseline, leading to the negative feelings when the drug wears off
dopamine in nuc acc.
go back to baseline levels
CRAVING
Rewarding properties -
Aversive properties -
Incentive Sensitization - focusses on a change in the positive feelings
Negative Allostasis - focusses on the negative, withdrawal side of addiction.
Incentive Sensitization:
- focusses on a change in the positive feelings
- with repeated administration, the positive addictive properties increase leading to an increase drive to keep taking the drug.
- in the beginning the drug is taking because people “like” it, with repeated dosing the liking changes into “wanting” which grows stronger with increased exposure to the drug.
Negative Allostasis:
- focusses on the negative, withdrawal side of addiction.
- with repeated administration the dysphoric withdrawal symptoms increase leading to an increase drive to avoid these symptoms.
Distinguish between “liking” and “wanting”
Over time, the wanting increases, while liking remains the same (or even diminishes)
This drives craving and relapse
Focus on withdrawal symptoms
Over time, the withdrawal symptoms increase
This drives craving and relapse
Drugs of abuse – Dopamine
Changes related to dopamine.
Acute reinforcing effectors (euphoria) come from the activation of dopaminergic cells in the VTA that projects to nuc acc – “liking” (decrease over time, increase of dopamine should be less)
Repeated drug use –activation of the dopaminergic system, mesolimbic system from the VTA to the nuc acc becomes less and activation of the nigrostriatal system from the substantia nigra to the dmCP and dlCP become stronger and stronger.
drug of abuse enhance dopamine in the cells from the ventral tegmental area (VTA) projection to the nucleus accumbens, with repeated administration, there is a shift towards increased dopamine release in the dorsomedial (dmCP) and dorsolateral caudate putamen (dlCP).
Drugs of abuse – Genetic Factors
Genetic alterations in the SERT is associated with….
Genetic alterations in the SERT is not associated
with…
Genetic alterations in the SERT is associated
with….
psychostimulant addiction
opioid addiction
alcohol addiction, but only in females
Drugs of abuse –Brain Mechanisms
Change in dopamine activity in the striatum, in chronic cocaine users is directly related to the self-reported high
Suggesting there is a shift from activation of the dopaminergic cells through the nuc acc to the striatum
There is a relationship between activation of dopaminergic cells and activation of the brain (relative metabolism in the frontal cortex, directly related to the amount craving).
Areas of the frontal cortex have strong control over the basal ganglia. The increase activation leads to a disconnection between the frontal cortex and basal ganglia
…
Drugs of abuse – Cortical Influence
Anterior Cingulate Cortex
Cocaine abusers are more affected (more brain activation) by cocaine movies and less by erotic movies than controls
