Neuroplasticity and Drug Abuse

Question 1

Drug seeking behaviour depends on

Answer 1

frontal lobe and deep nuclei networks

Question 2

Addiction cycle

Answer 2

Prefrontal cortex, basal ganglia, and extended amygdala
cycle of binge/intoxication, withdrawal/negative affect, and preoccupation/anticipation
cellular adaptations to neurocircuits, synaptic systems, and molecules facilitate the cycle

Question 3

Prefrontal cortex

Answer 3

controls executive function, self regulation, decision making, assignment of value, error monitoring
impaired DA and glutamate transmission
cannot resist strong urges, poor decision making

Question 4

Basal Ganglia

Answer 4

integrates motivational and executive circuits
fires dopamine reward network

Question 5

Extended amygdala

Answer 5

rewards lose motivational power, only using gives high energy reward
elevated DA in reward causes stress, dysphoria in amygdala ‘anti-reward’ network in absence of drug
continued drug use to avoid dysphoria

Question 6

Sympathetic signals

Answer 6

pupils dilate
reduced salivation
heart rate increases
bronchi dilate
constriction of blood vessels = increased bp
gastric secretion and movement decrease
pancreas and adrenal gland inhibited
intestinal movement lessens
bladder relaxes
produces ejaculation and orgasm

Question 7

Parasympathetic signals

Answer 7

pupils constrict
tear glands stimulated
increased salivation
heart rate decreases
bronchi constrict
gastric secretion and movement increase
pancreas becomes active
intestinal movement increases
bladder contracts
produces erection

Question 8

Lobes and regions

Answer 8

frontal, parietal, temporal, occipital
corpus callosum, thalamus, hypothalamus, pituitary, hippocampus, pineal, cerebellum, medulla oblongata, pons

Question 9

Striatolimbic reward circuit

Answer 9

controls hedonic tone: baseline level of dopamine being released constantly
links VTA, NAc, ventral pallidum via medial forebrain bundle
attention, expectancy of reward, disconfirmation of reward expectancy and incentive motivation

Question 10

SL pathway 1

Answer 10

descending myelinated pathway from anterior bed nuclei to ventral tegmental area pathway (likely glutamate driven)

Question 11

SL pathway 2

Answer 11

most important
ascending dopaminergic ventral tegmental area to nucleus accumbens pathway

Question 12

SL pathway 3

Answer 12

GABA/substance P/enkephalinergic nucleus accumbens to ventral pallidum pathway

Question 13

Cocaine, amphetamine, ecstasy - activation of reward in NAc

Answer 13

interfere with dopamine re-uptake in the NAc = increased dopamine levels

Question 14

Nicotine - activation of reward in NAc

Answer 14

depolarizes VTA dopaminergic neurons = increased firing = increased dopamine levels

Question 15

Opioids, GHB, benzos, cannabinoids - activation of reward in NAc

Answer 15

hyperpolarize VTA GABAergic interneurons = increased dopamine levels

Question 16

Evolutionary purpose of reward circuit

Answer 16

reinforce survival behaviours like feeding, drinking, sex, maternal/paternal behaviours, social interactions
hijacked by addictive drugs

Question 17

Nucleus Accumbens

Answer 17

located in basal forebrain striatum
pleasure centre, involved in motivation, cognitive processing of aversion, reward/reinforcement of drug-taking, translating emotional stimulus into behaviour/action
reciprocal projections with VTA, PFC, amygdala, hippocampus, and basal ganglia
pleasure, planning and inhibition of behaviour via PFC, brainstem, basal ganglia projections (memory)
interface between limbic and motor systems

Question 18

Ventral Tegmental Area

Answer 18

located in the midbrain
involved in cognition, motivation, locomotor activity
main driver of reward feelings
reciprocal projections with NAc, amygdala, raphe nuclei, PFC, basal ganglia…

Question 19

Prefrontal Cortex

Answer 19

in frontal lobe, extends into medial regions
self-awareness, conscious thought, planning, problem solving, learning, memory, executive functions, personality, decision making, social behaviour
reciprocal connections with multiple regions involved with attention, action, cognition

Question 20

Hippocampus

Answer 20

para-saggital plane, caudal amygdala
memory formation, processing novel and contextual information
contains neuronal stem cells - suppressed by drugs of abuse
VTA → hippocampus projections modulate plasticity and learning/memory

Question 21

Amygdala

Answer 21

emotions, learning, memory, reward, attention, arousal, stress
emotional reactivity (main driver of addictive cycle)
associates cues with drug consumption, conditioning, and reinstatement (re-lapse)
basolateral amygdala permits emotional regulation, decision making by medial PFC

Question 22

Caudate nucleus

Answer 22

voluntary movement, learning, memory, sleep, pain, social behaviour
reciprocal connections with VTA, NAc, hippocampus, and amygdala
where drugs accumulate and bind transporters

Question 23

Locus coeruleus

Answer 23

in dorsal pons
regulates arousal, cognition, memory, sleep-wake, attention, emotion, stress
stress - locus coeruleus norepinephrine afferents are modulated by kappa opioid receptor activation (NE is a stimulant - triggers fight or flight)

Question 24

Raphe nuclei

Answer 24

located in the dorsal medulla oblongata, multiple nuclei
regulate mood, emotion, aggression, sleep, anxiety, memory, appetite, pain, and temperature
nuclei an forebrain projections are targets of alcohol, opioids, MDMA and others

Question 25

Feelings of reward, motivation, anticipation/craving, euphoria, anxiety, fear, aggression

Answer 25

connection between NAc and VTA

Question 26

Associations between learning and memory

Answer 26

in the hippocampus

Question 27

Motivated behaviours - drug-seeking and taking

Answer 27

anticipation and craving - basal ganglia

Question 28

Impulsivity

Answer 28

deficient frontostriatal “top-down” cognitive control (inhibition in pre-frontal cortex)
= inability to override thoughts that lead to actions
mainly dorsolateral prefrontal activity

Question 29

The state effect

Answer 29

acute and chronic use change brain structure and function

Question 30

Compulsivity

Answer 30

tendency toward repetitive, habitual actions, repeated despite adverse consequences
decreased voluntary control over urges, inability to inhibit compulsive behaviours

Question 31

compulsive drug seeking behaviour

Answer 31

drugs of abuse elevate striatal dopamine - reinforcement
VTA → nucleus accumbens dopaminergic projections: reward circuit
frontal inputs (PFC): anticipation circuits
amygdala inputs: reinstatement/relapse circuits

Question 32

neuroplasticity

Answer 32

change through use: growth and reorganization
ability to form new connections, change wiring patterns of circuits, and establish new pathways

Question 33

neurotransmission

Answer 33

facilitated through the dendrites, somas, axons, and terminals of neurons

Question 34

action potential

Answer 34

firing of nerve when dendrites or soma reach threshold
causes release of neurotransmitters from terminals
short term ionic changes

Question 35

shape of neuron

Answer 35

made up by intracellular components of cell - cytoskeleton; filaments and tubules
maintain connections between neurons

Question 36

repeated neuron firing

Answer 36

sustained activity induces long term changes - cascades by triggered receptors
molecular signaling and transcriptional changes

Question 37

Addiction: shift from impulsive to compulsive

Answer 37

reward-driven behaviour shift to goal-driven
correlates to a ventral striatum to dorsal striatum shift in control of drug-seeking behaviour

Question 38

tolerance

Answer 38

taking more drug without feeling effects or needing more drug to feel same effects
cellular adaptations
metabolic - ex. cells in liver increase CYP enzymes to increase the metabolism of alcohol
behavioural - adapting to walk in straight line even while drunk

Question 39

withdrawal

Answer 39

direct consequence of tolerance
generally unpleasant affective moods and symptoms

Question 40

dependence

Answer 40

not the same as addiction
requiring drug to maintain normal physiological function (does not require psychoactivity)
triggered by tolerance/withdrawal