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Pharmcol > Lecture 2: The Brain (Neuroplasticity and Drug Abuse) > Flashcards

Lecture 2: The Brain (Neuroplasticity and Drug Abuse) Flashcards

1
Q

Ventral Tegmental Area (VTA)

A
  • 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
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2
Q

Nucleus Accumbens (Nac)

A
  • 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
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3
Q

Striatolombic

Mesolimbic Pathway
Striatal-Limbic Circuit

A
  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
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4
Q

Ventral Straitum

A
  • 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
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5
Q

Dorsal Straitum

A
  • located toward the top of brain
  • associated with motor control and habit formation
  • consits of caudate nucleus and putamen
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6
Q

Dependence

A
  • 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)
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7
Q

Withdrawal

A
  • 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
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8
Q

Tolerance

A
  • 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
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9
Q

Neuroplasticity

A
  • 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)
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10
Q

Neuroplasticity

PART 2

A
  • 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
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11
Q

Compulsivity

A
  • 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
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12
Q

Impulsivity

A
  • 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
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13
Q

Prefrontal Cortex (PFC)

A
  • 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
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14
Q

Hippocampus (Hippo)

A
  • 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
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15
Q

Amygdala (Amy)

A
  • 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
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16
Q

Caudate Nucleus (CN)

A
  • 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
17
Q

Locus Coeruleus (LC)

A
  • 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
18
Q

Raphe Nuclei (RN)

A
  • 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
19
Q

Craving

A
  • 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
20
Q

Anticipation

A
  • 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
21
Q

Striatolimbic Reward Circuit

THE MAIN TRAGET FRO FRUGS OF ABUSE

A
  • 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
22
Q

Striatolimbic Reward Circuit

MAIN TARGET FOR DRUG ABUSE

MORE INFO

A
  • 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
23
Q

Striatolimbic Reward Circuit

THE 3 STEPS

A
  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
24
Q

ALL ADDICTIVE DRUGS INCREASE DOPAMINE LEVELS IN THE NAc

A
  • 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
25
Q

Feelings, Associations & Motivated Behaviour

A
  • 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
26
Q

Impulsivity & Substance Use Disorders

A
  • 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
27
Q

Impulsivity & Substance Use Disorders

PART 2

A
  • 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
28
Q

Compulsivity Is Driven By Urges

A
  • 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
29
Q

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

A
  • 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
30
Q

Elevated Striatal Dopamine + Glutamate Potentiates New Goal-Directed Circuits

A
  • 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
31
Q

Drugs Induce Physiological Responses Too

A

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)
32
Q

Physiological Responses Are Subject To Pharmacological Tolerance, Withdrawal

A
  • 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
33
Q

Physiological Responses Are Subject To Pharmacological Tolerance, Withdrawal And Dependence

A
  • 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
34
Q

Sympathetic

A
  • 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
35
Q

Parasympathetic

A
  • 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

Pharmcol (5 decks)

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