Lecture 7/8- Alcohol Flashcards
What are the 2 distinguishing factors of drug associated harms?
-Harm done to users eg physical/dependence
-Harm done to others eg social
What did the 2007 criteria say about harm done by drugs?
Many of the highly regulated drugs eg LSD are lower in harm assessment.
Suggests how we deal with drugs may be skewed as legal drugs/alcohol are actually more harmful.
What improvements did the 2010 criteria make regarding harm done by drugs?
Involves 16 aspects not 10,
Scores from 0-100 not 0-3,
Differential weighting of criteria to indicate importance.
What are the 2 aspects of complex neuropharmacology?
Non- specific
Specific
What are the non-specific effects of alcohol?
(Neuropharmacology)
-Interactions with lipid bilayer; mainly at higher concentrations.
What are the specific effects of alcohol
(neuropharmacology)
Interaction with ligand-gated ion channels (i.e., neurotransmitter receptors) and voltage-gated ion channels; at concentrations within range achieved by common alcohol consumption
What is the First Hit regarding neuropharmacology and alcohol?
Acts on range of neurotransmitter receptors eg GABA, NMDA, excites inhibitor receptors so inhibits neural activity. This leads to cascade of synaptic events invol transmitters
How does alcohol affect levels of anxiety in humans?
Similar to classical anxiolytics, such as benzodiazepines, alcohol acts as indirect agonist at GABA-A receptors, eg enhances the response of the major inhibitory neurotransmitter GABA. (Harris & Mihic, 2004)
What two studies highlight anxiety reduction from alcohol in rats?
-Cat odour avoidance test
-Elevated maze test
What happened in the Cat odour avoidance test?
Rats put in cage and time taken to approach and time spent hiding was recorded.
As amount of beer increased, time spent hiding and approach time reduced.
What happened in the Elevated maze test?
Rats have an inherent fear of heights so it was recorded how long they spent in open air with differing amounts of alcohol.
Results found as alcohol levels increased, amount of time spent in open air also increase suggesting high confidence and lower anxiety levels.
How does alcohol induce memory loss?
Interferes w/ memory especially with encoding of new info into LT declarative memory.
-May range from minor memory lapses or ‘black outs’ with complete absence of memory
What are the 2 types of mechanisms involved in alcohol induced amnesia?
-State dependence
-Selective interference w/ hippocampus
What is State dependent alcohol amnesia?
-Information encoded/learnt in a drugged state, may be remembered better if tested in a comparable drugged state, then in a non-drugged state
eg more likely to find an object hidden during alcohol state when drinking alcohol again
What does Olverton (1964) study say about state dependence?
Alcohol has been shown to render some aspects of declarative memory state dependent.
There is also evidence for asymmetric state dependence as retrieval was especially reduced in the AS group, but less so in the SA group.
What is the Word association test in state dependent memory?
(Olverton, 1964)
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.
Results-Recall is better in group AA than AS which supports state-dependent recall as both encoded alcohol but retrieval type differs
How does Selective interference w /hippocampal memory mechanism affect alcohol induced amnesia?
Alcohol mainly interferes with encoding of new declarative information, similar to damage to the hippocampus (such as in patient H.M.).
Eg 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.
What happens in the baseline conditions of the LT potential?
-During baseline conditions, glutamate receptors only activated AMPA receptor as NMDA is blocked by magnesium in receptor sites
What happens in times of intense simulation of LT potential?
-In times of intense simulation, magnesium ions are expelled from NMDA receptors which increases amount of Sodium and Calcium ions into the synapse.
-Can lead to increase in AMPA receptors of increase in AMPA receptor efficiency which allow more current through.
What do dopamine rewards do in the meso-corticolimbic system?
Rewards activate dopamine transmission/release in nucleus accumbens, reduces activity of interneurons which stops reuptake and ultimately increases amount which drives process of addiction as you want to replicate feeling of high dopamine
What does alcohol dependence do to neural mechanisms?
Long-term compensatory changes in neural mechanisms in response to chronic excessive alcohol, which are opposed to acute effects of alcohol
What do LT compensatory changes contribute to regarding alcohol dependence?
-Tolerance in response to repeated alcohol use, i.e. reduced acute alcohol effects
-Chronic psychological changes when sober
What is withdrawal hyper excitability?
Altered balance between excitatory and inhibitory neurotransmission in response to chronic alcohol use.
What happens due to withdrawal hyperexcitability?
-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 the effects of withdrawal hyper excitability?
-Withdrawal symptoms eg seizures, tremors, cravings.
-Excitotoxic brain damage (LT cog defecits)
What happens during reduced dopamine transmission in withdrawal?
-Reduced nucleus accumbens dopamine during withdrawal. -Reduced spontaneous activity of dopaminergic neurons in the VTA
What are the effects of reduced dopamine transmission in withdrawal?
Reduced sensitivity to (natural) rewards and reduced motivation
What is the cognitive impairment associated w/ excessive alcohol?
Wenicke-Korsakoff syndrome
What is Wernicke-Korsakoff syndrome caused by?
Caused by thiamine deficiency, most commonly in association with alcoholism.
What is Wernicke-Korsakoff syndrome?
Acute stage, characterised by ophthalmoplegia (paralysis of eye muscles), confusion, ataxia.
What is 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
What does Wernicke-Korsakoff do in uncomplicated alcoholics?
May present with deficits in sensory-motor and executive functions, learning and memory and show marked fronto-cerebellar brain damage.
