Substance Abuse Flashcards
Substance abuse is a type of _______.
behaviour
Substance abuse is
the use of drugs in a non-prescribed manner or disapproved of by society. It could be recreation use (i.e. non medicinal drugs).
It is often associated with negative social and personal problems. It is not necessarily accompanied by dependence (e.g. social drinkers are not necessarily dependent on alcohol) BUT abuse carries a risk of dependence and/ or addiction
Dependence is a type of _____.
state
Physical dependence is
an altered state involving physical dependence when use of drug is suspended. Body NEEDS it in order to function to the new normal state. Can be intense. Can result in vomiting, nausea, headache
Psychological dependence is
a state involving drive requiring periodic or continuous use of drug in order to produce pleasure or avoid discomfort (withdrawal anxiety)
Addiction is a type of _______
disorder
Addiction is characterised by:
Treatment often requires
- abuse and dependence
- compulsive and uncontrollable drug seeking
- persistence in the face of negative consequences
- relapsing disorder
more than treatment of the dependent state
morphine, heroin:
primary target =
action on target =
mu opioid receptor
agonist
ketamine, PCP:
primary target =
action on target =
NMDA- receptor
blocks the ion channel
cocaine:
primary target =
action on target =
DA transporter
blocks reuptake
amphetamine, MDMA (ecstacy)
primary target =
action on target =
DA and 5-HT transporter
stimulates release and reverses action of transporter
alcohol:
primary target =
action on target =
ion channels
mimics glutamate antagonists and GABA agonists
nicotine:
primary target =
action on target =
nACh receptor
agonist
THC:
primary target =
action on target =
CB1 receptor
partial agonist
What are the four common behavioural actions of abused drugs?
- Subjective effects
- Reinforcing effects
- Tolerance
- Sensitisation
What are subjective effects?
ALL drugs of abuse produce subjective effects. These are feelings that are produced by drugs. It is one of the main reasons for drug abuse e.g. euphoria produced by opioids/ stimulants. However, subjective effects are not ALWAYS pleasurable e.g ketamine can produce euphoria & dysphoria. Subjective effect, itself, does not predict the addiction potential. e.g. k receptor agonist are not abused but can often ‘flag’ it up
Subjective effect; what role does it have in drug taking? There are 4 stages:
- initiation; curious about effects
- continued; desire to re-experience
- tolerance; euphoria produced by stimulants/ opioids leads to dose escalation, greater frequency
- internal cues; triggers contribute to bingeing, lack of control and craving for more drug.
What is polydrug abuse
This when drugs are mixed to enhance pleasurable effects or to reduce aversive effects. It creates a unique subjective experience and can be done by mixing stimulants and opioids
In pre-clinical studies, subjective effects are modelled using a technique called ____ ________
drug discrimination
Explain drug as reinforcers
Drugs are said to be reinforcers when they maintain a behaviour above the level obtained with placebo e.g. gin is a reinforcing drug because it maintains drinking behaviour above tonic alone
Positive reinforces are when the drug effects…
increase the likelihood that drug taking behaviour will occur
Positive reinforcement:
- Nature of reinforcing effect is positive
- Produces pleasure (rewarding)
- Other positive function e.g enhance attention, increase sociability.
Negative reinforcement:
Take a drug to avoid aversive consequence such as
- Withdrawal
- reduce craving
- obliterate reality (alcohol)
Are positive and negative reinforcements mutually exclusive?
NO! More than one mechanism can occur. Sometimes, the initial drug taking can be reinforced by positive mechanisms but as dependence develops, negative reinforcement mechanisms become important.
In pre-clinical studies, reinforcing effects are studied using a model called ____-________
self administration
Self-administration of drugs by animals suggests common _______________ mechanisms
neurobiological e.g
- neurochemical
- genetic
- structure/anatomy
Primary reinforcer is
something (food, drug) which increases the likelihood that a particular response will be repeated
Secondary reinforcer is
something that has power over the behaviour through ASSOCIATION with the primary reinforcer e.g money, or environmental objects
For addicts, tolerance to the subjective effects may lead to
dose escalation
What is sensitisation and when does it occur?
When there is an increased response to a drug (usually long lasting or permanent) Occurs from intermittent drug use.
With sensitisation, the dose response curve shifts to the?
left
What are some responses that can undergo sensitisation?
Toxic effects - convulsions e.g. with cocaine
Tolerance and sensitisation occurs at different rates depending on
the different effects of drugs
Duration difference between tolerance and sensitisation
Tolerance may be reversible or short lasting
Sensitisation is long lasting/ permanent
What is Intra Cranial Self Stimulation?
is the operant conditioning method used to create the BSR response. Brain stimulation reward (BSR) is a phenomenon in which direct stimulation of regions of the brain (medial forebrain bundle; MFB, in lateral hypothalamus to ventral tegmental area; VTA) through either electrical or chemical means is rewarding and can serve as an operant reinforcer. The stimulation activates the reward system and establishes response habits similar to those established by natural rewards such as food and water
Neurones of the ventral tegmental area (VTA) contain which NT?
Dopamine
Studies show that DA receptor antagonist can cause?
anhedonia (loss of pleasure)
can attenuate responding ICCC, food, sex
What are the Dopamine pathways in the brain?
- Nigro-Striatal
- Meso limbic
- Meso cortical
- Tubero infundibular
Reward pathway alone =
Reward system =
- Meso limbic pathway
- Meso limbic + Meso cortical
Nigro-striatal pathway is from
Substantia nigra - striatum
Meso-limbic pathway is from
VTA - nucleus accumbens/ amygdala
Meso-cortical pathway is from
VTA - frontal cortex
Tubero infundibulum is from
Hypothalamus to the median eminence
Dopamine release is said to be ______ ______ as there needs to be an act of self-administration - not just a consequence of primary pharmacology of the drugs
response contigent
In meso limbic pathway, morphine acts on mu receptors in VTA and inhibit GABA release (inhibitor) so now, DA concentrations in the _____ _____, _______.
nucelus accumbens , increase
From the table with all the substance and primary target, which of have an addiction potential and which increase accumbal dopamine release?
ALL have addiction potential and increase Accumbal Dopamine release EXCEPT for bremazocine which act on kappa opioid receptors
When addicts react to cues, it is know as
abstinent relapse
This type of relapse is studied in animals by using ________ models
reinstatement
What regions of brain are required for reinstatement?
amygdala and pre-frontal cortex
What are TTX microinjections?
Tetrodotoxin. TTX blocks Na channels and therefore nerve impulses. TTX reversibly inactivates regions by preventing nerve impulses.
Is DA the only NT involved in reward pathway?
NO! Glutamate also involved. Glutamate mediates changes in plasticity (tolerance/sensitisation - NMDA receptor). It is also involved in reactions to ‘cues’ as shown by animal reinstatement studies.
