DRUG DEPENDENCE: Neurobiology of addiction Flashcards
(38 cards)
What are the two main molecular targets for ethanol? [2]
GABAA and NMDA receptors
What are the three main molecular targets for cocaine? [3]
DA, NAd (nicotinamide adenine dinucleotide) and 5-HT uptake systems
What are the three main factors that determine the development of addiction? [3]
Environment
Drug-induced effects
Genes
Name 3 selected genes involved in the vulnerability to develop opiate or cocaine addiction [3]
OPRM: Mu opoid receptor
OPRK: kappa opoid receptor
OPRD: delta opoid receptor
Probably don’t need to know in loads of detail
Describe the results of of this experiment; where participants were given raclopride (a tracer) that binds to dopamine receptors.
When givien ampethamines what was the physioloigcal response for:
- those who experienced pleasure? [1]
- those who experienced unpleasantness? [1]
Pleasure: ligand was displaced more: greater release of endogenous dopamine
Unpleasant: ligand stay attached more: less release of endogenous dopamine
Describe the mesolimbic pathway that controls reward circuits in the brain [2]
Which NT controls this pathway? [1]
dopaminergic projection from the ventral tegmental area
to the nucleus accumbens is essential in reward and drug dependence
Describe the neurobiological mechansim underlying withdrawal [3]
If take drug (e.g. morphine) causes a release of dopamine from dopaminergic neuron from the VTA
Synapses onto nucleus accumbens
But nucleus accumbens has inhibitory synapses back onto VTA through release of GABA and dynorphin on kappa opoid receptors
Causes feelings of dysphoria due to reduced dopamine release
What are the three stages of addiction? [3]
Binge / intoxication
Withdrawal / negative affect
Pre-occupation
Describe the neuroplasticity of the brain during drug-seeking behaviour [6]
Brain connectivity changes occur during the development of
addiction; there is gradual involvement of many CNS structures
and several neurotransmitter systems:
- ventral tegmental area
- nucleus accumbens
- amygdala
- insula
- prefrontal cortex
- hippocampus
Other than dopamine, which NTs become implicated in drug addiction / drug tking behaviour? [2]
gaba; glutamate
State two changes to brain metabolism in cocaine addicts [2]
Reduced availability of dopamine D2 receptors
Reduced cortical metabolism in cocaine abusers
If an addict had an impaired ability to perform the following, which part of their brain is most likely to be affected? [1]
Attention and flexibility
Working memory
Decision making
Awareness and insight
Learning and memory
Salience attribution
prefrontal cortex
What is iRISA syndrome [1]?
Which 4 symptoms is addiction underpinned by? [4]
There is impaired response inhibition and salience attribution (iRISA)
Addiction is underpinned by
* intoxication
* bingeing
* withdrawal
* craving
Explain an example of how chronic drug abuse can alter gene expression and therefore change brain structure [1
Chronic drug use causes an increase in the expression of expression of ΔFosB gene
Fos family of transcription factors, accumulates within a subset of neurons of the nucleus accumbens and dorsal striatum
FosB functions as a type of sustained “molecular switch” that gradually converts acute drug responses into relatively stable adaptations that contribute to the long-term neural and behavioral plasticity that underlies addiction.
State the impact of spine density and dendrite branching due to cocaine [1] and morphine [1] abuse
Cocaine: increases spine density and dendrite branching
Morphine: Decreases spine density and dendrite branching
What is alchohol abuse for:
- men [1]
- women [1]
over 5 units a day for men
over 3 units a day for women
Describe the effects of acute [2] and chronic [1] alcohol abuse on the brain [1]
Acute alcohol ingestion:
* leads to depressed excitatory transmission
* potentiated inhibitory transmission
Chronic:
* Shrinkage of brain grey matter in alcoholic patients
Release of which molecule drives the physchomotor effect of MDMA use? [1]
5-HT release
Behavioural effects co-incide with time course of 5-HT release
Describe the physiological consequence of long term MDMA use [1]
Describe three effects of brain function from long term MDMA use [3]
MDMA:
- glucose metabolism reduces
- Causes decreased learning perfomance, recall, recall consistency
Describe 6 effects that occur from acute MDMA toxicity [6]
Temperature elevation
Disseminated intravascular coagulation
Rhabdomyolysis (blocked by dantrolene)
Increased renal reabsorbtion of water
Hyponatraemia
Cerebral oedema
Describe impact of long term MDMA use on axons in brain [1]
Loss of serotonin axons after long term MDMA use
Cannabinoids bind to [] and [] receptors
Main agonist present in cannabis preparations: []
Cannabinoids bind to CB1 and CB2 receptors
Main agonist present in cannabis preparations: THC
CB1 receptors are concentrated in the []
CB2 receptors are present in [] and are associated
with the [] system
CB1 receptors are concentrated in the central nervous system
CB2 receptors are present in peripheral organs and are associated
with the immune system
Describe the mode of action of cannabinids [1]
CB1 receptors are pre-synaptic & control how much glutamate / gaba is released
Cannabinoids, as neuromodulators, exert mainly inhibitory effects
