Lecture 8 - Alcohol 2 Flashcards
What is alcohol-induced memory loss (amnesia)?
- Alcohol interferes with memory, especially with the encoding of new information into long-term declarative memory
- Alcohol-induced anterograde amnesia may range from little memory lapses (‘cocktail party memory deficits’ e.g. can’t remember what they were talking about) to ‘fragmentary’ or ‘en block black outs’, i.e. partial or complete absence of memory, for experiences under alcohol influence, if large amounts of alcohol have been drunk rapidly (‘binging’)
What did the study by White et al. (2002) show about alcohol-induced memory loss?
- White et al. (2002) asked 772 undergraduates ‘have you ever awoken after a night of drinking not able to remember things that you did or places you went?’
- 51% of those who had ever consumed alcohol answered YES
- (Drinking in young people is actually reducing)
How may state dependence explain alcohol-induced amnesia?
- Information encoded/learnt in a drugged state, may be remembered better if tested in a comparable drugged state, than in a non-drugged state (Overton, 1964)
- Such state-dependence of memory may partly account for alcohol-induced amnesia
Describe evidence for/against the role of state dependence in alcohol-induced amnesia
- Experiments testing for state-dependence typically include 4 groups in a 2x2 design (AA, SS, AS, SA)
- Goodwin et al. (1969)
- Alcohol has been shown to render some aspects of declarative memory state dependent
- There is also evidence for asymmetric state dependence, i.e. retrieval was especially reduced in the AS group, but less so in the SA group
- However, state-dependency appears to account mainly for little memory lapses or fragmentary blackouts – en block blackouts seem to be due to other mechanisms (Goodwin, 1969)
Describe the state-dependent effect of alcohol on word-association memory
- Word-association test
- Learning phase (Day 1): subjects were asked to respond to 10 words with the first word that comes to mind
- Recall phase (Day 2): subjects were cued with the words and asked to recall their response from Day 1
- Difference between AA and AS groups is best explained by state-dependence
How may selective interference with hippocampal memory mechanisms explain alcohol-induced amnesia?
- Alcohol mainly interferes with encoding of new declarative information, similar to damage to the hippocampus (such as in patient H.M.)
- Thus, interference with hippocampal synaptic mechanisms of memory may contribute to alcohol-induced amnesia
- White (2003)
How does alcohol disrupt the induction of hippocampal long-term potentiation (LTP)?
- For example, alcohol disrupts the induction of hippocampal long-term potentiation (LTP) – an activity-dependent long-lasting increase in synaptic strength and a candidate physiological mechanism of memory (Bliss & Collingridge)
- At baseline, magnesium blockers prevent role of AMPA receptors
- Intense stimulation allows AMPA receptor to contribute to transmission (allows calcium ions, triggering intercellular mechanisms)
- Calcium influx increases AMPA receptor efficiency and number of receptors, making synapse stronger
What does the study by Givens and McMahon (1995) show about alcohol and LTP?
- Long lasting increase in synaptic stimulation
- Alcohol abolished long term potentiation
Many of alcohol’s effects are unpleasant, so why do so many people consume alcohol?
- Alcohol drives reward system, which motivates us to continue
- Rewards activate meso-corticolimbic dopamine transmission
- Release dopamine at projection sites
How does intracerebral microdialysis measure neurotransmitters?
- Put microdialysis probe in brain area of interest
- Flush fluid through – content of extracellular space and neurotransmitters e.g. dopamine can be measured
What have experiments using microdialysis shown?
Drugs of abuse (including alcohol) increase accumbal dopamine levels
- Alcohol is very rewarding -> triggers further use
What can excessive chronic alcohol use lead to?
Alcohol dependence
What characterises substance abuse?
Impairs functioning, legal problems, used dangerously, used despite legal, social or medical problems
What characterises substance dependence?
Development of tolerance, physiological/cognitive signs of withdrawal at abstinence, frequent desire/effort to reduce drug use, preoccupation with securing, consuming and recovering from drug (daily activities directed by drug)
How do neuropharmacological adaptations to repeated and chronic alcohol use contribute to dependence?
- Long-term compensatory changes in neural mechanisms in response to chronic excessive alcohol, which are opposed to acute effects of alcohol
- These contribute to:
- Tolerance in response to repeated alcohol use, i.e. reduced acute alcohol effects
- Chronic psychological changes when sober
What is withdrawal hyperexcitability?
- Altered balance between excitatory and inhibitory neurotransmission in response to chronic alcohol:
- Decreased GABA-A receptor function (compensating for acute GABA enhancing effects of acute alcohol)
- Increased glutamate receptor stimulation and function (compensating for decreased glutamate release and decreased NMDA receptor function in response to acute alcohol)
What are some possible effects of withdrawal hyperexcitability?
- Many withdrawal symptoms: seizures, tremor, withdrawal anxiety, alcohol craving
- Excitotoxic brain damage (resulting in long-term cognitive deficits) – if neurons are excited too strongly, they die
What happens to dopamine during withdrawal and what possible effect can this have?
- Reduced nucleus accumbens dopamine during withdrawal – dopamine transmission initially goes up after alcohol injection, then go lower than control during withdrawal
- Reduced spontaneous activity of dopaminergic neurons in the VTA
- Possible effect:
- Reduced sensitivity to (natural) rewards and reduced motivation
What causes Wernicke-Korsakoff syndrome?
- Caused by thiamine (vitamin) deficiency, most commonly in association with alcoholism
- Poor diet – get all calories from alcohol
What is Wernicke syndrome?
- Wernicke Syndrome: acute stage, characterised by ophtalmoplegia (paralysis of eye muscles), confusion, ataxia (lack of muscle coordination and control)
What is Korsakoff syndrome?
- Korsakoff Amnesia: remains after treatment of acute Wernicke Syndrome if thiamine deficiency lasted too long; global impairment in forming new declarative memory; severe brain ‘shrinkage’, especially striking degeneration of the mammillary bodies
- Mamillary bodies interact with hippocampus to form declarative memory
Describe cognitive deficits and brain shrinkage in ‘uncomplicated’ alcoholics
- Even alcoholics without WKS, may present with deficits in sensori-motor and executive functions, learning and memory and show marked fronto-cerebellar brain damage
How is brain shrinkage associated with moderate alcohol use?
- Negative associations between alcohol intake and brain macrostructure and microstructure are already apparent in individuals consuming an average of only one to two daily alcohol units, and become stronger as alcohol intake increases (Daviet et al., 2022)
- Only reduced brain volume by a very small amount (only evident with very large sample)
- Effects are reversible
