Effects of Alcohol Flashcards
What is the lethal blood alcohol level for 50% of people (LD50)?
0.4%
What are the non-receptor mediated effects of alcohol?
Presence of alcohol in the body disturbs membrane-bound proteins of cells
It interacts with the polar heads of phospholipids
and alters the lipid composition of the membrane
What does alcohol do to ionotropic glutamate receptors?
Alcohol is a non-competitive antagonist of NMDA and AMPA receptors
What does alcohol do to metabotropic glutamate receptors?
Alcohol is an agonist of group 2 mGlu receptors
What is NMDA?
A synthetic compound used by researchers to agonise the NMDA receptor
Not produced endogenously
What is the effect of alcohol on ionotropic glutamate receptors?
Blocks the receptor
Prevents influx of cations
Reduces excitatory neurotransmission
Effects are dose-dependent
Has no affect on the Mg2+ block
What is the effect of alcohol on metabotropic glutamate receptors?
Activates presynaptic mGlu2 and mGlu3
Inhibits VOCCs, preventing neurotransmitter release
Opens potassium channels, causing hyperpolarisation
What are the effects of chronic alcohol intake on glutamate receptors?
- Upregulation of NMDA and AMPA receptors
- Increased conductance of NMDA and AMPA receptors
- Decreased reuptake of glutamate from synaptic cleft by glial cells
- Desensitisation of mGlu group 2 receptors
What are the symptoms of alcohol withdrawal?
Seizures
Tremors
What causes symptoms of alcohol withdrawal?
Due to all the compensatory adaptations caused by chronic alcohol intake, when the alcohol is removed, there is excessive excitatory neurotransmission
What are the behavioural effects caused by acute alcohol intake, mediated by glutamate receptors?
Amnesia
What are the behavioural effects caused by chronic alcohol intake, mediated by glutamate receptors?
Seizures Anxiety Excitotoxicity Disorientation Brain damage Foetal alcohol syndrome
What effects does alcohol have on GABA-a receptors?
Alcohol is a positive allosteric modulator of GABA-a receptors
Increased ion channel conductance of chloride ions
Hyperpolarisation
Alcohol also causes release of neurosteroids, which are positive allosteric modulators of GABA-a receptors
What effects does alcohol have on GABA-b receptors?
Agonist of GABA-b receptors
Enhances GABA release - it is not entirely clear how this effect arises
What is the ‘tone’ of a neural circuit?
How easily a group of neurons is excited/inhibited
What are the effects of chronic alcohol intake on GABA-a receptors?
The GABA-a subunit composition changes, which decrease it’s sensitivity to alcohol and neurosteroids
The GABA-a receptors also change their localisation, from being present synaptically, to extra-synaptically
Alcohol has no affect on the GABA-a receptor number
What are the behavioural effects caused by acute alcohol intake, mediated by GABA receptors?
Reduced inhibitions
Reduced anxiety
Sedation
Impaired co-ordination
What are the behavioural effects caused by chronic alcohol intake, mediated by GABA receptors?
Alcohol tolerance
Tremors
Seizures
What are opioids?
Agonists of opioid receptors
Cause pain relief and anaesthesia
They can also be neuromodulatory, by reducing the effect of GABA interneurons
What are the types of opioids (and examples of each)?
Synthetic (codeine)
Endogenous (Endorphins)
Opiates (morphine, heroin)
What type of receptors are opioid receptors?
GPCR
What are the 4 main groups of opioid receptors?
Delta
Mu
Kappa
ORL1/Nociceptin
Where are opioid receptors found?
CNS, PNS and GI tract
How are opioids involved in dopamine release?
Opioids have a neuromodulatory (inhibitory) effect on GABA interneurons in the ventral tegmental area (VTA) in the midbrain
GABA interneurons inhibit dopamine release
What is the interaction between alcohol and opioids?
Alcohol enhances the effects of opioids
Increases GABA interneuron inhibition
Increases dopmaine release
Stimulates reward pathway
Alcohol also increases endogenous opioid synthesis
Example of an opioid receptor inhibitor
Naltrexone
Used to treat recovering alcohol/opioid addicts by decreasing their desire for alcohol or opioids, by dissociating the rewarding effect
What are the behavioural effects caused by acute alcohol intake, mediated by opioid receptors?
Euphoria
Reinforcement of behaviour - alcohol addiction
What are the behavioural effects caused by chronic alcohol intake, mediated by opioid receptors?
Dysphoria
What are the effects of chronic alcohol intake on opioids and opioid receptors?
Downregulation of opioid receptors
Reduced synthesis of endogenous opioids
What effects does alcohol have on glial cells?
Upregulates transporters on astrocytes, increasing the speed at which glutamate and other excitatory neurotransmitters are removed from the synaptic cleft
