lecture 34 Flashcards
1
Q
What are some particularly powerful determinants of behaviour?
A
- small molecules
- e.g.
- ethanol
- nicotine
- valium
- LSD
- cocaine
- heroin
- prozac
- caffeine
interesting that drugs/v small molecules work at all
2
Q
Why do people use recreational (or abused) drugs? What do these drugs provide to the user?
A
- pleasure
- hedonic drugs are typically addictive and users exhibit tolerance along with addiction
- novelty or unreality
- pyschedelic drugs are less commonly considered to be addictive (phencyclidine, betel nut, marijuana, caffeine, gamma-hydroxybutyrate, yage, psilocybin, and LSD)
- some drugs that are highly addictive (tobacco) are not associated with tolerance
3
Q
What aspects of brain function do these drugs affect?
A
- behaviour
- e.g. people who take opiates become extremeley vegetative - mental state
- motivation
- perceived salience
- meaning and significance
- arousal/vigilance
- hedonic experience (pleasure)
- emotional states and experiences
4
Q
Why do drugs work?
A
- must mimic some endogenous chemical interactions in the brain
- particularly between neurons
- neurotransmitters are also small but affect many aspects of behaviour
5
Q
What are psychoactive drugs?
A
- drugs with “mind altering” effects are called psychoactive
- these can, from a users point of view, be considered as either hedonic, psychadelic or stimulant
- many abused drugs appear to act by modulating neurotransmission at the synapses of the diffuse modulatory systems, particularly serotonin, dopamine and noradrenaline
- a well known psychedelic drug, LSD, is a hallucinogen, producing distortions of sensations and abnormal associations between sensory experiences
- in the 60s and 70s (when it was legal) it was widely promoted by users as being “mind expanding”
- the structure and pharmacology of LSD suggests it acts as a serotonin agonist, but its action is complex and not fully understood
- stimulants such as amphetamines and cocaine seem to act on aminergic transmission (noradrenaline and dopamine)
- howeber, heroin is a hedonic opiate the also modulations aminergic systems
- in much of the world, traditional mood-altering substances such as cocaine and heroin are in decline. But a pharmacopoeia of synthetic drugs is rapidly taking their place
- cumulative number of new psychoactive substances identified globally - over 300
- a lot of them haven’t been subject to any sort of drugs
- synthetic cannabinoids
- synthetic amphetamines
- ketamine is now a major part of drug economy
6
Q
Why are hedonic drugs addictive?
A
- the fundamental principle that unites addictive drugs appears to be that each enhances dopamine by means that dissociate it from normal behavioural control, so that they act to reinforce their own acquisition
- amphetamines affect dopamine: DAT substrate, VMAT substrate, MAO inhibitor, TH activator collapse of vesicular pH gradient
- cocaine: DAT blocker
- ethanol - maybe? possible disinhibition, addictive property is probably
- nicotine: nAChR agonist
- opioids: µ opioid receptor agonists
- sedatives: GABAa receptor coactivators benzodiazepines/agonists
- solvent inhalents: unclear, may enhance release probability
7
Q
Why do drugs work in subtle ways?
A
- if not, too much damage to brain
- act via metabotropic coupled receptors which modulate the excitability
- few percent difference rather than on/off
- clearly more complicated because doesn’t affect whole brain etc
8
Q
Of what is paranoia a symptom?
A
- common symptom in schizophrenic illness
- also can be side effect of medication or recreational drugs such as marijuana
- particularly stimulants such as methamphetamine and crack cocaine
9
Q
What is the projection that makes drugs addictive?
A
- VTA to nucleus accumbens
10
Q
What is the biggest drug problem?
A
alcohol
- 2 billion users of alcohol, world wide
- WHO estimates worldwide that 3.2% of deaths and 4% of total years of life lost are caused by alcohol abuse ( and most preventable)
- the annual cost of alcohol-caused problems in Australia has been estimated to be 4.5 billion dollars (about 2.6 times the cost for illicit drugs)
- about 2/3 of the costs are alcohol dependence-related
11
Q
What is invovled in alcohol consumption and outcome?
A
- patterns of drinking average volume
- toxic and beneficial biochemical effects
- intoxication
- dependence
- chronic disease
- accidents and injuries (acute disease)
- acute social and psychological problems
- chronic social and psychological problems
12
Q
What is chronic alcohol related disease?
A
- cancer (mouth and oropharyngeal, oesophageal, liver, breast)
- neuropsychiatric diseases (AUDs, unipolar major depression, epilepsy)
- diabetes, cardiovascular diseases
- gastrointestinal diseases (cirrhosis of the liver)
- conditions arising during the perinatal period
13
Q
What are examples of common comorbid conditions?
A
- medical conditions such as malnutrition and diseases of the liver and the cardiovascular system
- neurological conditions such as head injury, inflammation of the brain (i.e. encephalopathy), and foetal alcohol syndrome (or foetal alcohol effects)
- psychiatric conditions such as depression, anxiety, post-traumatic stress disorder, schizophrenia, and the use of other drugs (Petrakis et al. 2002)
14
Q
What is the mechanism of action of alcohol?
A
- know big picture and small picture but not how they link together
- acts on GABA-gated Cl- channel (GABAa receptor)
- ethanol is an agonist and an antagonist
15
Q
What are the acute effects of alcohol on the brain?
A
- the literature on the mode of action on brain excitability and neurotransmitter interactions is complicated and incompletely resolved
- alcohol is claimed to both potentiate and antagoise GABA’s effects (which can be used to explain sedation and disinhivition response)
- chronic alcohol consumption decreases GABA receptor density in the brain - which is consistent with anxiety (and the use of benzodiazepine) in alcohol withdrawal
- alcohol has been show to interfere with glutamate action
- chronic alcohol consumption increases glutamate receptor sites in the hippocampus, an area that is crucial to memory
- alcohol directly stimulates release of the neurotransmitter serotonin, which is important in emotional expression, and of the endorphins, natural substances related to opioids, which may contribute to the “high” of intoxication and the craving to drink
- alcohol also leads to increases in the release of dopamine (DA), a neurotransmitter that plays a role in motivation and in the rewarding effects of alcohol
