Lecture 2: The Brain (Neuroplasticity and Drug Abuse)

Question 1

Ventral Tegmental Area (VTA)

Answer 1

• located in the midbrain
• involved in cognition, motivation, locomotor activity
• main driver of rewarding feelings
• reciprocal projection (two brain regions are closely connected and can influence each others activity) with NAc (Nucleus Accumbens), Amy (Amygdala), RN (Raphe Nuclei) PFC (perfrontal cortex), basal ganglia and others

Question 2

Nucleus Accumbens (Nac)

Answer 2

• located in basal forebrain striatum
• pleasure centre, involved in motivation, cogition, processing of aversion, reward/reinforment of drug-taking, translating emotional stimulus into behavior/action
• reciprocal projection (two brain regions are closely connected and can influence each others activity) with VTA (ventral tegmental area), Amy (Amygdala), Hippo (hippocampus), PFC (perfrontal cortex), basal ganglia and others
• pleasure, planning, and inhibition of behavior via PFC, brainstream, basal ganglia projections (implications for memory)
• interface ebtween limbic and motor systems

Question 3

Striatolombic

Mesolimbic Pathway
Striatal-Limbic Circuit

Answer 3

1. dopaminergic athwayin the brain that connects the ventral tegmental area (VTA) to the limbic system, including the nucleus accumbens
   - pathway associated with reward, pleasure, and motivation
   - drugs influence the acivity of this pathway = leading to feelings of euphoria and reinforcing drug-seeking behavior
2. involved in motor control and reward processing (striatum)
   - plays a role in emotions and motivation (limbic system)
   - processes the rewarding effects of drugs and reinforces drug-seeking behavior

Question 4

Ventral Straitum

Answer 4

• key component of the basal genglia
• plays crucial role in various and cogitive functions
• located toward the bottom of the brain
• linked to reward, motivation, and emotional processing
• included nucleus accumbens (role in processing pleasurable eperiences, reinforcng behaviors, and mediating the effacts of drugs) as its central component

Question 5

Dorsal Straitum

Answer 5

• located toward the top of brain
• associated with motor control and habit formation
• consits of caudate nucleus and putamen

Question 6

Dependence

Answer 6

• rely on a drug to function normally
• feeling like you need the drug to feel okay
• Physical or psychological (emotional) symptoms when drug is absent
• body and mind have become used to the drug (dependent on the drug)

Question 7

Withdrawal

Answer 7

• uncomfortable painful symptoms that occur when a person stops using a drug they have become dependent on
• symptoms: physical and psychological discomfort (cravings, anxiety)
• opposite of drug effect the symptoms
• like taking mediaction to help with sleeping then stop taking the medication the withdrawal symptom would be insomina
• bodies way of reacting when it’s used to the having a certain drug and doesn’t get it anymore

Question 8

Tolerance

Answer 8

• body gets used to a drug
• no longer the same effect it used to, might need to take more of the drug to have the same desired effect
• body became less responsive to the drug need to take higher dosage of it
  OR
• taking more and more of the drug without feeling the effects

Question 9

Neuroplasticity

Answer 9

• brain to change and adapt in response to the drugs
• change through use: growth and reorganization
• form new connections
• change wiring patterns and establish new pathways
• brains flexibility to reorganize its structure and functions when exposed to certain substances
• can involve the strengthening/weakening of connections between nerve cells (can affect how the brain processes information and responds to drugs)

Question 10

Neuroplasticity

PART 2

Answer 10

• Main neuronal structures → dendrites, soma,
  axon, terminals (DSAT)
• These structures facilitate neurotransmission
• When dendrites or soma reach threshold, nerve
  fires = action potential
• Release of transmitters from terminals
• Intracellular components makeup the shape of the
  neuron
• Short-term ionic changes
• Repeated firing induces long-term changes via
  molecular signaling and transcriptional changes

Question 11

Compulsivity

Answer 11

• refers to a strong and difficult to control urge or behavior related to the use of drugs
• person feels compelled to take a drug (even if they don’t want to and know its not good for them)
• can lead to repetitive and often harmful actions associated with drug use

Question 12

Impulsivity

Answer 12

• a collection of multideensional behaviors (incorporate state and trait classifications)
• acting quickly without thinking carefully (espically when it comes to taking drugs)
• hasty decisions or taking a drug on a whim without condsidering the conseqences
• lead to risky behaviors and drug use without much thought or planning

Question 13

Prefrontal Cortex (PFC)

Answer 13

• located in frontal lobe (extends into medial region)
• self-awarness, planning, problem solving, learning, memory, executive functions, personality, decision making, social behavior
• PFC–> VTA +Amy expression of behaviors trained by chronic drug abuse
• reciprocal connections with multiple regions involved with attention, action, cognition
• vastly integrated with multiple regions dsyfunctions underlies several mental conditions (ex: bipolar, schizophrenia)
• uses memory to guide ebhavior and attention
• intense emtions, impluese, surpresses emotionl urges

Question 14

Hippocampus (Hippo)

Answer 14

• located in para-saggital plane, caudal Amy
• memory formation, processing novel and contextual information
• contains neuronal stem cells, surpressed by drugs of abuse
• drugs enhance LPT and LTD
• VTA –> Hippo projections modulate plasticity and learning/memory

Question 15

Amygdala (Amy)

Answer 15

• emotions (fear, pleasure), learning, memory, reward, attention, arousal, stress
• key involvement emotional reactivity, most disabling symptom in addicts
• associaties cues with drug consumption, conditioning, reinstatement
• chronic drug abuse disrupts Amy –> PFC connections
• basolateral Amy permits emotional regulation, decision making by medial PFC

Question 16

Caudate Nucleus (CN)

Answer 16

• voluntary movement, learning, memory, sleep, pain, social behavior
• reciprocal connections with VTA, NAc, Hippo, Amy
• lesions alter chronic effects of drug abuse
• drugs accumulate here, bind transporters

Question 17

Locus Coeruleus (LC)

Answer 17

• located in the dorsal pons
• regulates arousal, cognition, memory, sleep-wake, attention, emotion, stress
• projects to VTA, brainstem, cerebellum,
• thalamus, hypothalamus, hippo, Amy, basal ganglia, cortex and spine
• stress - LC-NE afferents are modulated by K opioid receptor activation
• might regulate a number of withdrawal symptoms, target for therapy

Question 18

Raphe Nuclei (RN)

Answer 18

• located in the dorsal medulla oblongata, multiple nuclei
• regulate mood, emotion, aggression, sleep, anxiety, memory, appetite, pain and temerature
• Projects to hypothalamus,
  limbic system, brainstem,
  spine
• Nuclei and forebrain
  projections are targets of
  alcohol, opioids, MDMA and
  others
• RN→PFC projections have
  implicated RN in neuropsychiatric disorders: OCD, ADHD, schizophrenia and others

Question 19

Craving

Answer 19

• strong and intense desire or longing for something (like food)
• when you really want something and it is hard to resist/ignore the urge to have it

Question 20

Anticipation

Answer 20

• expectation of the effects or outcomes of a drug
• idea or sense of what the drug will do (waiting for those effects to happen)
• feeling of knowing what to expect

Question 21

Striatolimbic Reward Circuit

THE MAIN TRAGET FRO FRUGS OF ABUSE

Answer 21

• reward circuit controls hedonic tone (ability to feel pleasure)
• releasing baseline dopamine at all times (no sensations)
• reward circuit = 3 inseries pathways linking VTA, NAc, ventral pallidum via medial forebrain bundle
• attention expectancy of reward, disconfirmation of reward expetancy and incentive motivation

Question 22

Striatolimbic Reward Circuit

MAIN TARGET FOR DRUG ABUSE

MORE INFO

Answer 22

• plays role in how you feel pleasure and reward
• a pathway in your brain that makes you feel good when you do things you enjoy
• encourages you to repeat behaviors that bring pleasure but can be a target of addiction, when abusing drugs
• the drugs release of dopamine in this circuit (leading to intense feelings of pleasure and a strong desire to sue drug again)
• affects attention and what you do when you feel

1. VTA: pleasure center
   - contains cells that release neurotransmitter called dopamine (feel good chemical and associated with pleasureable sensation)
2. NAc: reward center
   - VTA sends dopamine signals to the NAc
   - ex: when doing something pleasurable or rewarding (like eating tasty food), VTA releases dopamine, and it travels to the NAc
   - this dopimine release makes you feel good and reinforces the behavior that led to the pleasure, encouraging you to do it again
3. Ventral Pallidum: involved in regulating and modulating the pleasure response
   - after the NAc the signals continue to the ventral pallidum

Question 23

Striatolimbic Reward Circuit

THE 3 STEPS

Answer 23

1. path goes from one to another (VTA) and carries signals using a chemical called glutamate (helps create feelings of reward and pleasure)
   - descending pathway from anterior bed nuclei to VTA which is glutamate driven
2. another part of your brain send messages through this pathway to a place called the nucleus accumbens (delivery of special cemical called dopamine (linked to feeling really good))
   - VTA to NAc (dopaminergic)
3. from NAc, theres another path that goes to a place called ventral pallidum (diiferent chemicals like GABA, substance P, and enkephalin that play a role in controlling your feelings of pleasure

• when drugs used they can be either speed up or slow down the traffic on these paths (making you feel intense pleasure or cravings)
• reward circuit that fires to produce pleasurable feelings, there is also an nti-reward system that is counterbalancing that

Question 24

ALL ADDICTIVE DRUGS INCREASE DOPAMINE LEVELS IN THE NAc

Answer 24

• differnt drugs activate reward at different sites within circuit
• cocaine, amphetamine, ecstasy interfere with dopamine re-uptake in the NAc
• Nicotine depolarizes VTA dopaminergic neurons
• Opioids, GHB, benzos, cannabinoids hyperpolarize VTA GABAergic interneurons
• reward circuit evolved to reinforce survival ebhaviors like feeding, drinking, sex, maternal/paternal behaviors social interactions
• addictive drugs hijack reward circuit

Question 25

Feelings, Associations & Motivated Behaviour

Answer 25

- reward, motivation, anticipation/craving, euphoria, anxiety, fear, aggression - learning and memory - drug-seeking, drug taking - initially, drug-taking behaviour is reward-driven - impulsiveness vs compulsiveness

Question 26

Impulsivity & Substance Use Disorders

Answer 26

- Impulsivity is a collection of multidimensional behaviours → incorporate state and trait classifications * Measures of impulsivity rely on self-reports, behavioural scores and electrophysiology * Results in a spectrum manifestations * Deficient frontostriatal “top-down” cognitive control- an inability to override thoughts that lead to actions * Dorsolateral prefrontal activity mainly involved

Question 27

Impulsivity & Substance Use Disorders ## Footnote PART 2

Answer 27

- Reduced thought and judgement before acting * High association between impulsivity and incidence of SUDs * Trait effect of impulsivity mostly made up of decreased cognitive and response inhibition * The state effect → acute and chronic use change brain structure and function * Genetic and environmental factors influence the course of impulsivity in SUDs

Question 28

Compulsivity Is Driven By Urges

Answer 28

- Compulsivity refers to a tendency toward repetitive, habitual actions, repeated despite adverse consequences * Along with: * Decreased voluntary control over urges * Diminished ability to delay or inhibit compulsive behaviors * A tendency to perform repetitive acts in a habitual or stereotyped manner

Question 29

Repeasted Administration Of Addictive Drugs Can Lead To Compulsive Drug-Seeking Behaviour

Answer 29

- All drugs of abuse elevate striatal dopamine which reinforces drug-taking behaviours - VTA → NAc DA-ergic projections are at the core of the reward circuit - Many addictive drugs lose their euphoric effect, e.g. tobacco - Frontal inputs are at the core of anticipation circuits, e.g. PFC * Amy inputs are at the core of reinstatement/relapse circuits

Question 30

Elevated Striatal Dopamine + Glutamate Potentiates New Goal-Directed Circuits

Answer 30

- Dopamine and glutamate are critical neurotransmitters - Addiction starts as occasional recreational use then impulsive use then habitual compulsive use * Reward-driven to goal-driven drug-seeking behaviour - Correlates with a ventral striatum-to-dorsal striatum-mediated shift in control of drugseeking behaviour

Question 31

Drugs Induce Physiological Responses Too

Answer 31

CNS: Brain and Spinal Cord (PNS: nerves that go to and from the CNS) (two ways) 1. AFFERENTS - Sensory Division (nerves going into the CNS) (two ways) Somatic Nervous System - sensations from touch, pain, vision, hearing, balance, smell Autonomic Nervouse System - sensations from the viscera about hunger, nausea, taste, internal pain 2. EFFERENTS - Motor Division (nerves going out from the CNS) (two ways) Somatic Nervous System - voluntary control of skeletal muscle movement Autonomic Nervouse System (two ways) - Sympathetic Nervous System (fight/flight) - Parasympathetic Nervous System (business as usual)

Question 32

Physiological Responses Are Subject To Pharmacological Tolerance, Withdrawal

Answer 32

- Tolerance → cellular, metabolic and behavioural * Taking more drug without feeling effects or needing more drug to feel the same effect * Withdrawal → generally unpleasant affective moods and symptoms * Due to tolerance/dependence

Question 33

Physiological Responses Are Subject To Pharmacological Tolerance, Withdrawal And Dependence

Answer 33

- Dependence and addiction are not the same, but overlapping * Many drugs induce dependence without addiction e.g. anti-hypertensives * Addiction is triggered by reward circuit activation + neuroplasticity in other regions * Dependence is triggered by tolerance/withdrawal e.g. pain reduction by opioids in the periaqueductal grey

Question 34

Sympathetic

Answer 34

- pupil dilates - reduced salivation - heart rate increases - bronchi dilate - constricts blood vessels and increases blood pressure - gastric secretion and movement decrease - pancreas and adrenal gland inhibited - intestinal movement lessens - bladder relaxes - produces ejaculation and orgasm

Question 35

Parasympathetic

Answer 35

- pupil constricts (tear glands stimulated) - increased salivation - heart rate decreases - bronchi constrict - gastric secretion and movement increases - pancreas becomes active - intestinal movement increases - bladder contracts - produces erection