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Biopsych - Psychopharmacology (Y1) - Coggle Diagram
Biopsych - Psychopharmacology (Y1)
What is a psychoactive drug?
An exogenous chemical, not required by the organism for normal function, and the drug significantly changes the cellular process of a neuron
Two important concepts -
pharmacokinetics - the movement of the drug in the body in terms of its absorption, distribution, metabolism and excretion
-> Half life - the amount of time it takes for the drug to reduce 50% of its starting concentration in the blood
After one half life, the concentration of the drug in the body will be half the starting dose
Pharmacodynamics - the effects of a drug on the body and behaviour
-> potency - amount of drug needed to produce an effect of a certain magnitude
-> Efficacy - a drug's ability to produce an effect
Psychopharmacology - study of drugs and their impact on behaviour, cellular function and cognitive function
How do drugs affect the central nervous system - psychoactive drugs can affect all stages in the lifecyle of a neurotransmitter
Production - conversion from precursors; drug is the precursort
Storage - drug disrupts it
Release - drug inhibits release
Binding - drugs bind to a receptor to trigger processes or binds to the receptor as a blocker
Deactivation (facilitate / suppress removal, producing more enzyme and reduce the production of enzymes = less removal) - drug disrupts reuptake and drugs suppress certain enzymes
Psychoactive drugs cause measurable behavioural/physiological changes
In order for a psychoactive drug to have any actual effect, it must get into the brain by passing through the blood brain barrier
the function of the blood brain barrier is to protect the brain, acting as a strong filter
For a drug to actually have any effect, it has to meet this criterion
Can affect all stages in the lifecycle of a neurotransmitter - resultant effects can change brain functions and human behaviours
Learn about how they are digested, metabolised, cleared from body
Pharmacodynamics - how it changes mind and behaviour
Pharmacokinetics - how it enters, travels and exits
Drugs that impinge on dopamine
Levodopa -L-DOPA; dopamine in motor control, L DOPA for treating Parkinson's as it is caused by a loss of dopamine neurons; patients have difficulty initiating movements, leading to treatment to compensate for the loss
L DOPA used as treatment
Pharmacodynamics - dopamine is made from L-DOPA - can cross the blood brain barrier and enzymes can convert the precursor into dopamine
Dopamine level increases in the brain
Leads to a relief from symptoms, compensating for the loss of dopamine neurons
Not a cure - side effects are common
Patients have to deal with the side effects of hallucination, delusion or other symptoms
Antipsychotic drugs and dopamine - psychotic disorders are characterised by hallucination and delusion - this medication is a treatment
Antipsychotic medication operates by interfering with dopamine receptors, essentially acting as a blocker
Schizophrenia is caused by an excess of dopamine
An excess of mesolimbic dopamine is thought to be a culprit of the disorder, and thus drugs that block dopamine can reduce symptoms
Pharmacodynamics - antipsychotic drugs work by blocking the D2 receptor - reducing operation of the dopamine system and efficacy hinges on the ability to bind to this receptor
A positive correlation - better binding, better treatment
Side effects - antipsychotic drugs cannot specifically target the mesolimbic pathway which can affect motor function (rigidity and spasms)
We can treat motor control problems of Parkinson's by increasing the level of dopamine in the nigrostriatal pathway with L DOPA but this can trigger hallucinations and delusion by mistakenly increasing dopamine levels in the mesolimbic pathway
We treat the hallucinations and delusions of schizophrenia by blocking the dopamine receptors in the mesolimbic pathway with antipsychotic medications, but antipsychotics can mistakenly block dopamine receptors in the nigrostriatal pathway
We cannot only target one pathway, and medicines therefore have a blanket effect across many regions where dopamine receptors exist, causing unwanted side effects
Recreational drugs that rely on dopamine
Involved in producing reward and pleasure - cocaine; used as a stimulant for religious and social purposes, and as a folk medical treatment; Native Americans chewed it to reduce hunger, fight fatigue and enhance physical performance
Medical uses as a local anesthetic - and used to relieve attitude sickness, and Freud was a main promoter of cocaine after it was synthesised for the first time in 1859, and popularised in the 1880s calling it a magical substance
In 1886, Pemberton included coca leaves in Coca-cola which was removed in 1903 as the physical and psychological side effects became known, and cocaine was banned in 1922
Cocaine - short term effects - increased energy, decreased appetite, mental alertness, increased heart rate and blood pressure, constricted blood vessels, increased temperature and dilated pupils
Long term effects of cocaine - addiction, irrationality and mood disturbances, restlessness, paranoia and auditory hallucinations
Medical consequences of cocaine abuse - cardiovascular effects of disturbance in heart rhythms and heart attacks, respiratory effects of chest pain and respiratory failure, neurological effects of strokes and seizures and headaches and gastrointestinal complications of abdominal pain and nausea
Molecular processes -
Works by increasing dopamine levels in the brain - it does this by inhibiting the reuptake of dopamine
After the release, neurotransmitters return to the presynaptic neuron -> reuptake
When a presynaptic neuron is reuptake DA, the molecules of DA diffuse back to the opening called a transporter (DAT - dopamine active transporter)
Cocaine blocks the transporter opening, closing the passage
Cocaine therefore prevents the transporter doing its job and absorbing the DA, meaning levels remain high
Amphetamines - works on dopamine system with similar effects
physical effects of improved reaction time, fatigue resistance, increase muscle strength, mood improvement, reduced appetite, increased wakefulness, anxiety, irritability, restlessness, and unwanted alertness, and helps you stay awake, energised and attentive
At higher doses - risk of psychosis and addiction, risk of seizure, strokes, comas and heart attacks
Applied as treatment for depression, rarely prescribed nowadays due to a high risk of physical / psychological harm (widespread in 20th century)
Pharmacodynamics - on the dopamine system but in a different way
Causes neuron to release more DA, whereas cocaine disrupts the reuptake - after binding, amphetamine drugs disrupt the storage of dopamine in the vesicles, and the cell is then filled with DA, triggering the neuron to spew out dopamine
As a result of the drug, dopamine is released without the triggering of action potentials
Compared to cocaine - less euphoric but more stimulating, due to different modes of action, pharmacodynamics, but both increase dopamine signalling in the major pathways
Similarity between the two - increased dopamine signalling in the mesolimbic pathway, this is what underlies gratifying and addictive qualities of both these drugs
The mesolimbic pathway is a key circuit of reward and pleasure in the brain
Increased dopamine signalling in the nigrostriatal pathway, leading to enhanced basal ganglia and thalamic activity - increased motor activity (hyperlocomotion) leading to users feeling energised, tremoring etc
Drugs that act on serotonin - SSRIs - selective serotonin reuptake inhibitors
Commonly prescribed to treat depression and anxiety
Pharmacodynamics - it works by inhibiting the reuptake of serotonin by blocking the transporter that draws back serotonin into the neuron; blocking the transporter means more serotonin in the synapse, it is the most commonly prescribed medication despite efficacy still being questioned
Pharmacokinetics - fluoxetine half life is 1-4 days
MDMA (ecstasy) - key difference between this and an SSRI is that SSRI prevents the reuptake of serotonin and ecstasy triggers the neuron to release more of it
Pharmacodynamics - it enters the cell via the passage of serotonergic transporter and triggers the release of serotonin and also effects norepinephrine and dopamine transports - indirectly increases hormones such as oxytocin
Pharmacokinetics - duration of action is 4-6 hours, after which serotonin levels in the brain are depleted and serotonin levels normalise with 24-48 hours
Hallucinogens - a drug that can cause distortion in a person's perception of reality can cause changes to thoughts, moods and consciousness
Hallucinogens work on serotonin receptors as they can trigger subsequent effects like real neurotransmitters usually do
Wide range of drugs with hallucinogenic properties, either natural or synthetic
Includes - LSD (acid), Psilocin (magic mushrooms), mesacline (peyote cactus), DMT (ayahuasca)
Other major psychoactive drugs
Nicotine -
pharmacodynamics - nicotinic receptor is one of the two receptors that ACh can bind onto, nicotine binds to this ventral tegmental area
After nicotine binds to the neurons in the VTA, it leads to neural activity that triggers the release of dopamine in the mesolimbic pathway
CNS - pleasure, arousal, enhanced vigilance, improved task performance, anxiety relief
Cardiovascular system - heart rate increase, increase BP, increase cardiac output, vasoconstriction cutaneously and coronary
Other - highly addictive, increased metabolic rate, skeletal muscle relaxation
Pharmacokinetics - half life of 30 minutes, leading to rapid elimination; smokers metabolise faster, gender differences in nicotine metabolism - 16-25% of the population with a genetic defect which leads to an inability to metabolise nicotine, and can be protected from being a smoker
Smoking is a major risk factor for heart attacks, strokes, bronchitis, cancers, high blood pressure and Alzheimer's disease, nicotine is highly addictive
Reward from mesolimbic dopamine release leading to addiction
Inhaled through smoking or vaping, long term smokers vulnerable to lung cancer or respiratory infections and Buerger's disease (vasoconstriction of leg blood vessels)
Those who live with smokers can also develop high risks for these diseases, and foetus is also at risk - transgenerational epigenetics
Caffeine - most widely consumed stimulant on the planet - pharmacodynamics - molecule of caffeine is similar in structure to adenosine, which is a inhibitory neurotransmitter
By binding to the adenosine receptors instead, caffeine prevents the inhibitory effects of the adenosine happening, therefore reducing inhibition and making you more awake and energised
Increases release of other neurotransmitters (dopamine, serotonin acetylcholine and epinephrine)
Pharmacokinetics -
Caffeine is absorbed within 45 minutes, rapidly distributed through the body
Molecules are small enough to cross the blood brain barrier
Half life varies according to a person's liver enzyme level (caffeine level usually drops below 50% within 3-7 hours)
Some people are more sensitive to caffeine than others, and are a more efficient metabolism due to their enzymes
Cannabis / Marijuana - THC; Tetrahydrocannabinol -
Pharmacodynamics - bind to cannabinoid CB1 receptor - widely distributed throughout the brain primarily in the mesolimbic pathway
once the THC binds to the CB1 receptor, it triggers the release of dopamine
Mesolimbic dopamine release leads to the feeling of euphoria
Potential medical benefits - some people suffer from chronic pain - cannabis acts as a painkiller
Can be as effective as opioids
Patients in palliative care can have a better quality of life if they use cannabis to relieve discomforts
Long term habitual cannabis use - associated with decline in memory function, and the longer you smoke it regularly, the more brain tissue loss
Alcohol - ethanol - pharmacodynamics - how it funtions at a cellular level is still poorly understood
Wide spectrum of physiological and cognitive effects on the mind/ body
Generally classified as a depressant because it suppresses neural activities in the CNS
The mechanism is that alcohol triggers the release of GABA, leading to the brain being in a sedation state
It increases the release of dopamine in the mesolimbic pathway - euphoric qualities of alcohol
Not limited to just one neurotransmitter - the mechanism of alcohol entails GABA, dopamine, glutamate, adenosine and others
Pharmacokinetics - alcohol can easily cross the blood brain battier by diffusion, metabolised by liver, transformed into water, CO2, and about 2-10% if excreted unchanged in sweats, breaths and urine
Health risks of long term heavy drinking - Korsakoff syndrome; a chronic memory disorder in which there are persistent learning and memory problems (retrograde and anterograde amnesia) and difficulty with action coordination
Loss of brain volume - heavy alcohol use is linked to brain shrinkage, particularly evident in prefrontal lobes, and light to moderate drinkers are not at risk with shrinkage possibly being reversible with abstinence
Withdrawal - first phae is 6-8 hours after and is characterised by anxiety, tremor, nausea and tachycardia, second phase beings 10-30 hours after and has hyperactivity, insomnia and hallucinations.
Third phase between 12-48 hours and is characterised by convulsive activity
4th phase begins 3-5 days after the cessation of drinking and lasts up to a week, called delirium tremens (DT) characterised by disturbing hallucinations, bizarre delusions, disorientation, agitation, confusion, hyperthermia and tachycardia (can be lethal)
Foetal alcohol syndrome - baby will also go through this
The opioids: morphine and codeine - exert effects on receptors whose normal function is to bind to endogenous opioids - endorphins and enkephalins
opioids can be effective analgesics (painkillers) and they are extremely effective in the treatment of coughs and diarrhoea, but they are highly addictive
Used for euphoric effects and pain for years
Heroin - more potent analgesic than morphine but less likely to cause vomiting and nausea
Many people fall victim to opioid overdose due to synthetic drugs such as fentanyl and oxycodone - more potent and addictive than heroin
Opioid withdrawal is as bad as the flu
Main direct effects are constipation, pupil constriction, menstrual irregularity and reduced sex drive
Transgenerational epigenetic effects - children born from opioid addicts have severe withdrawal symptoms and display decreases in synaptic plasticity
Theories of addiction, the role of dopamine and mechanisms of drug tolerance:
Drug use - taking a psychoactive substance for non-medical purposes, which is often for fun or out of curiosity
Drug abuse - drug use that leads to problems (e.g. a dramatic decline in terms of quality of life, criminal behaviour and a loss of wellbeing)
Drug dependence - it refers to the situation in which you need more and more of the same drug to give you good feeling, because the initial small dose is no longer enough
Tobacco and alcohol are extensively used and both are moderately addictive
Marijuana is also widely used but only a small proportion of users will become addicted
Only a few people use or become addicted to harmful drugs
Theoretical models of addiction -
biological factors of hereditary, brain physiology, biochemical factors and intervention through medications to alleviate addictions
Personality traits - psychodynamic factors (id impulses, oral fixation) and defence mechanisms - psychoanalysis as treatment
Family dynamics - family dysfunction - family therapy
Associative learning - modelling or expectanices - positive role models, rational restructuring of expectancies
Societal environment - environmental, cultural and economic - social policy and social services
Three stages in the development of an addiction
Initial drug taking - not everyone given access to the drug will consume them, and those that do may not take it more than once (price, availability, peer pressure, life experiences are all factors)
People treat drugs as tools or instruments - they start using it if it benefits them in some way e.g. stimulants to keep you awake, alcohol for social interaction and sexual intercourse, self medication of THC
Habitual drug taking - using addictive drugs regularly - positive incentive does not explain why people become habitual and others do not, as fails to explain hedonic (like) and positive incentive (wanting) values of their drug - hedonic is actual pleasure experience, positive incentive is the pleasure associated
addicted individuals are compulsively driven to take their drug, but pleasure does not match this
Incentive sensitisation theory - discrepancy between hedonic and positive incentive - positive incentive value of the drug increases with repeated usage, making them motivated to consume it, but their anticipated pleasure of taking the drug is the wanting and craving of it
But, they gain tolerance for the pleasurable effects according to contingent drug tolerance - so the anticipated pleasure does not match actual pleasure, but they are compelled to consume it
Mesocorticolimbic pathway dopamine release in the nucleus accumbens is associated with wanting, rather than liking
Changes in brain function associated with transition from initial to habitual drug taking - striatum of drug addicts and striatal control is taken from NA (ventral striatum) to the dorsal striatum which is associated with habit formation
Paired with impairment in prefrontal cortex, which results in a loss of self control that accompanies addiction - causes other general behaviorual issues, such as inability to refrain from adverse effects behaviour, excessive risk taking, deficits in self control, overeating, compulsive gambling, kleptomania, compulsive shoppimg)
Experience anhedonia - inability to feel pleasure in response to natural reinforcers - prevents addiction being treated as they go back to it in order to feel something
Drug craving and relapse - three causes of this - many therapists and patients point to stress as a major factor in relapse
Drug priming - single exposure to formerly misused drug, feel they are in control, try it again and relapse
Exposure to cues - people, time, places or objects have previously been associated with drug taking has been shown to precipitate relapse
Conditioned compensatory responses seem to increase craving in abstinent drug addicted individuals and this triggers relapse (thinking about a drug is enough to relapse)
Drug associated cues presented later are more likely to elicit craving and relapse than cues presented later - incubation of drug craving
Environmental enrichment after drug withdrawal has reduced cue and stress induced relapse but not drug primed relapse
Even a few brief exposures to non drug reinforcers can reliably reduce relapse of cocaine self administration
Psychopharmacology of addiction - the brain's dopamine reward system:
The reward system relies on the mesolimbic pathway from the VTA to the ventral striatum
From a survival point of view, this system is triggered by stimuli that help humans to survive, as an individual or whole species
For example, food, water and sex - these things can produce enjoyable feelings and pleasure motivates us
The reason we crave more is because the dopamine system is involved in producing the feeling of reward and pleasure - it is important to note that drug addictions utilise the same dopamine mechanisms
How do drugs reinforce addictive behaviour? Dopamine release usually occurs as a response to important environmental stimuli such as food, for our survival
But addictive drugs can also trigger mesolimbic dopamine release
These drugs leads to higher levels of dopamine release than what a normal stimuli could trigger
Drugs hijack the reward system and cause an unnaturally large amount of dopamine release - this leads to seeking more of them to feel the same thing again
Amphetamine can generate a dopamine boost that's much higher than what we can see from eating a nice meal - food triggers dopamine, but not as extremely or potently as amphetamines
Using fMRI to study drug abuse - can reveal brain activity associated with drug use
Put volunteers in an MRI scanner, recording their brain activity following drug use
Region's activity sigificantly increased after the volunteers took cocaine, and those regions are in the mesolimbic pathway, including the VTA
The more euphoric they felt, the more activation of the mesolimbic pathway
Contribution of learning and memory to addiction - learn associations between drugs and other related things
With repeated use of a drug, drug addicts learn the multi-way associations between drugs, people, environments and a euphoric feeling
All these people and places become cues which include the addicted persons to engage in more drug misuse - conditioning to drugs
In MRI, showing drug addicts the photos of needles or powders is sufficient to induce mesolimbic activation, without the need to take the actual drug
Leaving bad environments and bad friends is crucial
Drug withdrawal effects - if you take addictive drugs regularly and then suddenly stop, you wil have these effects; severe headache, fever and chills
Negative reinforcement - you keep doing the behaviour you hate in order to avoid uncomfortable withdrawal symptoms
Tolerance - drug addicts take a higher dose in order to get the same level of euphoria, and the dose keeps going higher as a result of long term habitual use
Early theories of addiction explained it to be a physical dependence - people are trapped in a cycle of drug taking and withdrawal, with drug users whose intake has reached a sufficient level to induce physical dependence are driven to avoid withdrawal
Early addiction treatments attempted to break this cycle - highly addictive drugs however do not produce as much withdrawal distress and so this cycle does not make much sense
Drug taking also often follows a system of binges and detoxification due to jobs and money
Positive incentive theories of addiction - addicted individuals take drugs not to escape or avoid the unpleasant consequences of the withdrawal, but rather to obrain the drug's positive effects - primary factor in most cases of addiction is the craving for this
intracranial self stimulation and the mesotelencephalic dopamine system:
Brief bursts of weak electrical stimulation to specific sites in ones own brain and the brain area that mediate this ICC phenomenon are called pleasure centres
MDS - important role in ICC and is a system of dopaminergic neurons that project from the mesencephalon into various regions of the telencephalon; the neurons that compose this are made of the VTA and the substantia nigra
Most of the dopaminergic neurons that have their cell bodies in the substantia nigra project to the dorsal striatum and this component of the nigrostriatal pathway degenerates to cause Parkinson's disease
Mesocorticolimbic pathway - dopamine system that mediates intracranial self stimulation - many brain sites at which this occurs are in this pathway
ICC associated with increases in dopamine release in this pathway
Dopamine agonists tend to increase intracranial self stimulation and dopamine antagonists tend to decrease it
Lesions of the mesocorticolimbic pathway disrupt the ICC
Nucleus accumbens - events occurring here and in the dopaminergic input to it from the VTA appeared to be most closely associated with the experience of reward and pleasure
Four findings from research on lab animals that focused attention on this area
Lab animals self administer microinjections directly to this site
Microinjections of addictive drugs into the NA produced a conditioned place preference
Lesions to either the NA or the VTA blocked self administration or the development of conditioned place preferences
Both self administration and experience of natural reinforcers found to be associated with elevated levels of extracellular dopamine from the NA
How we observe dopamine in addiction - drug self administration paradigm (press a lever to inject drugs) and the conditioned place-preference paradigm (repeatedly receive drug in one compartment, drug free animal placed in a box with a neutral compartment as well, prefer drugged one)
Dopamine is important in the role of rewarding effects of addictive drugs and natural reinforcers, with dopamine findings suggesting that dopamine signals a reward value or pleasure
Concerns with drug self administration paradigm - unnatural housing and testing conditions and excessive focus on stimulants
Locations of the dopaminergic systems -
mesocortical pathway; Located from the VTA to cortex - planning and memory, motivation and emotional response
mesolimbic pathway - located from tegmentum (VTA) to nucleus accumbens in the ventral striatum - reward and pleasure system
Nigrostriatal pathway - located from substantia nigra to basal ganglia - concerned with movement; degeneration of this pathway leads to Parkinson's disease
Tuberoinfundibular pathway - located off hypothalamus towards pituitary gland - regulation of prolactin release leading to maternal behaviour
Basic principles of drug action
Drug administration, penetration and absorption into the central nervous system -
Administered through oral injection, injection, inhalation or absorption - route of choice impacts rate and degree to which the drug reaches its site of action
Oral - takes effect sooner due to absorption through digestive tract villi into blood
Injection - straight into veins, strong fast and predictable making it good for clinical settings
Inhalation - through lung capilliaries; hard to regulate dosage and can result in lung damage
Absorption through mucous membranes - some drugs are taken through these membranes of the mouth, nose and rectum, but this damages the membranes
Drug action, metabolism and elimination - once it enters the bloodstream, it is carried to the blood vessels of the CNS with the BBB protecting the brain from potentially dangerous blood borne chemical passing from the vessels of the CNS into the extracellular space around the CNS neurons and glia
Mechanisms of drug addiction - some psychoactive drugs influence the nervous system in many ways - with other drugs acting diffusely on neural membranes throughout the CNS and others in a more specific way of binding to synaptic receptors and influencing the transport, synthesis, release or deactivation of a particular neurotransmitter
Or they influence the reactions cause by postsynaptic receptors being activated
Drug metabolism and elimination - most drug actions are terminated by liver enzymes which then stimulate the conversion of active drugs to inactive forms - drug metabolism
Eliminates drug's ability to pass through lipid membranes of cells so that it cannot penetrate the blood brain barrier, and other small amounts are passed out through urine, sweat, faeces, breath and mother's milk
Drug tolerance - decreased sensitivity to a drug developed through repeated exposure to it - shown through a given dose having less effect than before or by showing it takes more of the drug to have the same effect; shift in the dose-response curve
One drug can produce tolerance to drugs with the same mechanism - cross tolerance
Drug tolerance can develop to some effects of a drug but not all - becoming tolerant to nausea does not make you tolerant to fainting - tolerance to some effects can cause drug sensitisation to others
Drug tolerance is not a unitary phenomenon - no single mechanisms that underlies it
Metabolic drug tolerance - drug tolerance that results from changes that reduce the amount of the drug getting to its sites of action
Functional tolerance - drug tolerance from changes that reduce the reactivity of the sites of action to the drug
Tolerance to psychoactive drugs is largely functional, and results from several different types of adaptive neural changes
e.g. reduces number of receptors for it, decreasing efficiency of binding with existing receptors or diminish the impact of receptor binding on the activity of the cell - epigenetic mechanisms
Drug withdrawal and physical dependence: sudden elimination causes an adverse physiological reaction of withdrawal syndrome which is opposite to the drug effects
Symptoms being opposite suggests that withdrawal is produced by the same neural changes that produce drug tolerance, with exposure to the drug producing compensatory changes in the nervous system that offset the drug's effect and produce tolerance (with no drug to offset, neural changes manifest as withdrawal opposite to initial effects
Severity of symptoms depends on the drug, duration of drug exposure and the speed at which it is eliminated
Drug addiction - habitual drug users who continue to use a drug despite its adverse effects on their health and social life and despite repeated efforts to stop cannot
Misconception - people believe drug addicts sit in a cycle of taking the drug to prevent withdrawal; but this is not normally the main motivation, as some do take them to avoid withdrawal but this could be solved by hospitalisation - as many renew their drug use after enforced abstinence this is likely not the case
All addictions are based on similar mechanisms
Contingent drug tolerance - refers to demonstrations that tolerance develops only to drug effects that are actually experienced - most studies of this employ a before and after design
In this, two groups of subjects receive the same series of drug injections and same series of repeated tests, but subjects in one group receive the drug before each test and others receive it after
All subjects then receive the same dose followed by a final test to that the degree to which the drug disrupts performance in the two groups can be compared
Pinel, Mana and Kim (1989) - injected rats with alcohol every 2 days for the duration of the experiment, and in the tolerance development phase the rats in one group received each alcohol injection an hour before a mild convulsive amygdala stimulation so the anticonvulsant effect of the alcohol could be experienced - other group received theirs an hour after
All subjects then had an injection 1 hour after the test on the final test to compare the amount of tolerance to the anticonvulsant in both groups
The rats who received alcohol before felt no effects, whereas those with the same injections and stimulations in reverse developed no tolerance
Conditioned drug tolerance: demonstrations that tolerance effects are maximally expressed only when a drug is administered in the same situation in which it has been previously administered
Crowell, Hinson and Siegel (1981) - two groups of rats received 20 alcohol and 20 saline injections in alternating sequence - one injection every other day
One group received all 20 alcohol injections in the test room and 20 of saline in the colony room, with the other group vice versa
tolerance to hypothermic effects of alcohol was assessed in both environments - tolerance only observed when rats were injected in the environment previously paired with alcohol administration
Situational specificity of drug tolerance - effects have been measured in generalizable, large, reliable ways
Drug users may therefore be more susceptible to the lethal effects of a drug overdose when it is administered in a new context, as the theory states that users become tolerant if administering in the same environment, and thus start having larger doses
They then change environments but keep the same dosage, and as the environmental effects do not cause tolerance, overdose can occur
Siegel (1982) - evidenced with heroin-tolerant rats moved into a new environment
Pavlovian concept of conditioning - environmental stimuli act as conditioned stimuli for the conditioned response of tolerance, so when the unconditioned stimulus of the drug is introduced to a new environment, there is no response for drug tolerance
Most demonstrations of conditioned drug tolerance uses extroceptive stimuli (external) as conditional stimuli, but introceptive are also important
Thoughts and feelings from the drug taking ritual and drug effects experienced soon after administration can, through conditioning, come to reduce the full impact of a drug can evoke conditioned compensatory responses
Compensatory responses and withdrawal effects are similar - both are opposite to unconditioned effect of the drug - drug withdrawal is caused by removal, conditioned compensatory responses are elicited by drug predictive cues in the absence of the drug
Drug sensitisation - can be situationally specific - a problem with drug addiction theories is that conditional stimuli can have responses similar to the drug
Ramsay and Woods (1997) - much of the confusion about conditioned drug effects stems from misunderstanding of Pavlovian conditioning; particularly, the unconditional stimulus in a drug tolerance experiment being the drug and the unconditional responses are whatever changes in physiology or behaviour the experimenter happens to be recording
unconditonal stimulus is instead the disruption of neural functioning that has been directly produced by the drug and the unconditional responses are the various neurally mediated compensatory responses to the unconditional stimuli
The conditional is always similar to the unconditional - determining the stimuli determines the response