Addiction & Brain Flashcards
What are neurones?
- The building blocks of the central nervous system (CNS)
- Responsible for receiving, processing and transmitting information throughout the body
- Roughly 86 billion in the human brain
- Responsible for cognition, sensory processing, motor control & coordination
What are neurotransmitters?
- Chemical messengers that transmit signals between neurons to other neurons across a synaptic cleft
- Presynaptic neurone – synaptic cleft – postsynaptic neurone
- Neuropeptides: (subset of neurotransmitters) typically more complex and have longer lasting effects compared to traditional neurotransmitters
Classic neurotransmitters: 4 examples
- Dopamine - cocaine (reward/excitement)
- Noradrenalin – cocaine (alertness/excitement)
- Serotonin - MDMA (happiness/love)
- Acetylcholine- nicotine (focus/memory)
Drugs & Synaptic transmission
- Agonist: typically involves binding to a receptor and activating it (mimicking a neurotransmitter)
- Antagonist: typically involves binding to a receptor and not activating it (blocking a neurotransmitter)
- Autoreceptors: these allow the neuron to self-regulate releasing or not-releasing, so things don’t get flooded (homeostasis)
Evidence of neurochemicals in addiction:
(Gerra et al 2000)
- PRL = prolactin (pituitary hormone)
- Fenfluramine promotes 5-HT release (used clinically to treat obesity, here to test 5-HT function, 5-HT regulates PRL)
- Long term: the drug itself is no longer present, but long-term effects are found
- Issues: little dose knowledge from MDMA users (only 100% in animal studies), people tend to underreport doses
Evidence of stress in addiction:
(Miczek & Mutschler 1996)
- Rats trained to respond for cocaine or food reward
- ‘Social stress’ = 60 mins as an intruder in the cage of a resident rat (protected from attack by a wire mesh)
- Issues: cause and effect issues
- Results: rats sought out cocaine over food once in a stressful situation
- Suggests selective effects of social stress on cocaine-reinforced responding
- Clinical reports suggest role of stressful life events in relapse, but these are correlational. Controlled animal studies can show cause and effect
What are catecholamines?
Catecholamines:
- They are psychomotor stimulants (e.g. dopamine, noradrenaline, serotonin, acetylcholine)
- Neurotransmitters and hormones derived from the amino acid tyrosine
- They play key roles in the body’s stress response, regulation of the blood pressure, heart rate, and various metabolic processes
- Tyrosine has something to do with dopamine synthesis
Hacking catecholamines
- A = potential to bond at receptor site
- B = full agonist
- C = antagonist (drug attaches but no response triggered)
- Cocaine: inhibits DA & NA transporters
- Amphetamines: increased DA & NA release
- Risperidone: blocks DA receptors (used in bipolar/ schizophrenia treatments)
- Ritalin: blocks DA & NA uptake (i.e. ADHD)
Indirect agonist: 2
(Bloomfield et al 2016)
- THC promotes DA release through cannabinoid receptors
- Long term DA system dulling
(Reigel et al 2007)
- Same results
- They are interacting with the systems that interact with dopamine levels
What is reserpine?
- General catecholamine antagonist
- Inhibits VMAT, a protein responsible for moving them into vesicles
- Test: injected rabbits with the drug
- Results: quite dramatic behavioural effects that follow their manipulations when we interfere with these process (e.g. become lethargic)
Dopamine pathways: 4 types
- Neural circuits through which dopamine travels to regulate various physical and psychological functions
- These pathways are critical for processes like movement, reward, motivation, emotion, and hormonal control
- A) mesocortical
- B) mesolimbic
- C) nigrostriatal
- D) tuberoinfundibular
Dopamine pathway: Mesocortical
- Regulates cognition, decision-making, emotion, and social behaviour
- Originates in the ventral tegmental area (VTA) but projects to the prefrontal cortex
- Dysfunction or underactivity is associated with negative systems or schizophrenia and cognitive impairments
- Drugs = target the mesocortical dopamine pathway that primarily aim to modulate dopamine activity in the prefrontal cortex
- These drugs are used to address cognitive dysfunction, ADHD, depression, and schizophrenia
Dopamine pathway: Mesolimbic
- Involved in reward, motivation and the feeling of pleasure
- This pathway plays a central role in reinforcing behaviours and the development of addiction
- Originates in the ventral tegmental area (VAT) and projects to the nucleus accumbens and other limbic areas (e.g. amygdala & hippocampus)
- Overactivity in this pathway is linked to addiction, positive symptoms of schizophrenia and other disorder’s involving reward processing
- Drugs = target the mesolimbic dopamine pathway primarily aim to modulate dopamine activity in the rewards and motivation system of the brain
- These drugs are commonly used to trat schizophrenia, addiction, depression, and Parkinson’s disease
- High dopamine in the mesolimbic pathway = psychosis, addiction, mania
- Low dopamine in the mesolimbic pathway = depression, anhedonia, apathy
Dopamine pathway: Nigrostriatal
- Controls movement and motor planning by facilitating the interaction between the basal ganglia and other motor control systems
- Starts in the substantia nigra and projects to the striatum (caudate nucleus and putamen)
- Degeneration of neurons in this pathway is a hallmark of Parkinson’s disease, leading to tremors, rigidity, and bradykinesia
- Overactivity can contribute to involuntary movements seen in conditions like tardive dsykinesia
- Drugs = crucial for motor control and used for Parkinson’s disease, drug-induced movement disorders, and Huntington’s disease
- Low dopamine = Parkinson’s, drug induced
- Excess dopamine = tardive dyskinesia, Huntington’s chorea
Dopamine pathway: Tuberoinfundibular
- Regulates in the secretion of prolactin from the anterior pituitary gland, playing a role in hormonal control
- Originates in the hypothalamus and projects to the pituitary gland
- Dysfunction can result in hyperprolactinemia, leading to symptoms such as infertility, sexual dysfunction and galafactorrhea (milk production)
- Drugs = DA acts as a prolactin antagonist
- Increase prolactin = infertility, menstrual irregularities decreased libido
- Decreased prolactin = rare and usually not clinically significant unless in conditions like hypopituitarism
How do we target drugs?
- DA has multiple receptors (e.g. multiple locks work for the same key)
- Some activate easily (D3), and others less so (D1)
- Some excite the neuron (D1-like), while others calm in down (D2-like)
- Location in different regions (e.g. D1 is key for motivation and movement, while D3 is more involved in addiction and impulse control)
Beyond drugs: 2 studies
(Giros et al 1996)
- From birth, not CRISPA edited
- Heterozygous = 1 deletion
- Homozygous = double deletion
- ABOVA shows double deletion = more active. The dopamine transporter would usually remove the dopamine
- An animal under treatment to become more hyperactive will respond by wanting more of that treatment, suggesting its rewarding and showing addicting potential
(Xu, Guo, Vorhees & Zhang 2000)
- Mutant mice lacking D1 receptors are insensitive to cocaine which increased locomotor activity in the wild-type but not the knockout mice
Patterns of drug use: Past
According to earlier British Crime Surveys (BCS):
- In 1996, around 30% of adults had tried illegal drugs at some point in their lives
- In 1998, this increased slightly to around 32%
- By 2000, it was around 33% (1 in 3 adults)
Patterns of drug use: Now
- UK: 38% of adults aged 16-59 have tried drugs
- USA: the national survey on drug use and health 2022 reports that over 50% of adults aged 12+ have tried an illicit drug at some point in their lives
- UK 2024: 8.8% of adults (16-59) reported using drugs
- USA 2022: 17.3% of Americans 12+ using illegal drugs
Key facts of drug use
- Drug use is relatively stable overtime
- Most illicit drug isn’t daily
- Most drug use is by younger people
- Most drug use is by less affluent people
- Most drug use is by men
- Use patterns vary by drug and age
- PCP (e.g. angel dust a dissociative anaesthetic)
- Salvia (herb in Mexico that produces hallucinogenic experiences)
Exposure models: Key features
- Most models of addiction are exposure models
- All people are at risk of becoming addicted to drugs given sufficient exposure
- Drugs interact with and change the brain
- Brain changes create continued motivation to use the drug
- Models differ in their explanation as to what sort of changes drugs produce in the brain and what sort of motivation drives subsequent drug use
- Focus on withdrawal
Withdrawal: key features
- Addicts continue to use the drug to avoid withdrawal
- The initial high exhausts the reward/pleasure regions of the brain and once the drug wears off the user goes into withdrawal (VERY aversive)
- A form of negative reinforcement
Withdrawal model issues: Relapse
- Stopping drugs under medical supervision does not necessarily result in long term abstinence
- Drug users often relapse despite having undergone supervised withdrawal from drugs
- Wikler (1948) proposed that withdrawal can be triggered by external cues
- Environmental stimuli such as the addict’s bedroom is consistently paired with withdrawal
- Through pavlovian conditioning, stimuli enter learned associations to become triggers for withdrawal symptoms
- Subsequent exposure to these cues is then sufficient to elicit withdrawal and thereby precipitate relapse
- Thus, conditioned withdrawal can explain relapse following primary withdrawal
- Anecdotal reports from relapsed drug users suggest things are not always as predicted e.g. by contexts in which withdrawal had occurred most frequently
- People can associate cues with outcomes over a delay or a trace (lingering effect of drugs)
Withdrawal model issues: can’t all be aversive
- Midbrain dopamine cells increase activity when humans or animals detect or consume both natural rewards (food, water, sex) and drugs of abuse (nicotine, cocaine, heroin)
- Suggest that drugs of abuse hijack the brain substrate for reward/pleasure and are consumed because drug taking is positively reinforcing