Neuropharmacology of Addiction Flashcards
What are the 2 types of dependence?
Psychological –> Craving, compulsive use, loss of control
Physical –> When stopping a drug causes a withdrawal syndrome (physical symptoms)
This can be caused by some non-rewarding drugs also
What do Kappa agonists do to dopamine levels?
Decrease them….so cause dysphoria
How does ethanol decrease hyperpolarization?
Acts as a K+ channel blocker
How is it proposed that alcohol increases the chance of opitate ODs?
Reverses opioid tolerence by reversing mu-opioid receptor desensitisation
Also possible for gabapentin to do the same
What are the 3 current categories of drug treatment for addiciton?
Substitution therapy –> NRT and OST
Aversion Therapy –> Use of disulfiram to prevent ethanol ingestion. This causes a build up of acetaldehyde….but complaince is a huge issue!
Antagonists/Antibodies –> Naltrexone/Buprenorphine are currently used, but several downsides
Antibodies are a devloping field…but a vaccine-like treatment could be possible!
What are the 3 major stimuli for relapse in humans?
Taking a small dose of the drug
Stress
Being presented with a cue that’s associated with taking the drug (eg, going to the pub)
What is the role of dynorphin in withdrawal?
Dynorphin –> A kappa agonist…so causes dysphoria
Dopamine binds to D1 receptors that are Gs coupled, causing an upregulation of certain factors like dynorphin. These cause GABA to inhibit dopaminergic neurones, whilst the dynorphin binds, causing a decrease in dopamine release
Why is there a link between D2 receptors and addiction?
Lower levels of D2 receptors = More dopamine needed for a euphoric effect
This can occur due to an SNP in a specific gene
Drug abuse can also cause a reduction in D2 receptors
Why are D2 antagonists not the answer to drug abuse?
As they would compete with dopamine, causing less to bind….so addicts would just use more illict drugs to overcome the block!
How could we try to make addicts forget that they are addicted?
By inhibiting synaptic plasticity during re-consilidation of a memory
So exposing the person to the memory (eg, the pub), and giving a drug (like propranolol) to weaken the memory
An ethical nightmare! And it isn’t very selective….
What are the following drugs?
Buproprion (Zyban)
Bromocriptine
Buproprion (Zyban) –> A DNRI that has a role in addicition treatment purley because of its antidepressent properties
Bromocriptine –> A D2 partial agonist
Only seems to work in those with lower levels of D2 receptors
Name two drugs that could help prevent stress related relapse
Antalarmin –> CRH-1 receptor antagonists
Mifepristone (Morning-after-pill) –> Glucocorticoid receptor antagonists
