Neuroplasticity and Drug Abuse Flashcards
Drug seeking behaviour depends on
frontal lobe and deep nuclei networks
Addiction cycle
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
Prefrontal cortex
controls executive function, self regulation, decision making, assignment of value, error monitoring
impaired DA and glutamate transmission
cannot resist strong urges, poor decision making
Basal Ganglia
integrates motivational and executive circuits
fires dopamine reward network
Extended amygdala
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
Sympathetic signals
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
Parasympathetic signals
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
Lobes and regions
frontal, parietal, temporal, occipital
corpus callosum, thalamus, hypothalamus, pituitary, hippocampus, pineal, cerebellum, medulla oblongata, pons
Striatolimbic reward circuit
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
SL pathway 1
descending myelinated pathway from anterior bed nuclei to ventral tegmental area pathway (likely glutamate driven)
SL pathway 2
most important
ascending dopaminergic ventral tegmental area to nucleus accumbens pathway
SL pathway 3
GABA/substance P/enkephalinergic nucleus accumbens to ventral pallidum pathway
Cocaine, amphetamine, ecstasy - activation of reward in NAc
interfere with dopamine re-uptake in the NAc = increased dopamine levels
Nicotine - activation of reward in NAc
depolarizes VTA dopaminergic neurons = increased firing = increased dopamine levels
Opioids, GHB, benzos, cannabinoids - activation of reward in NAc
hyperpolarize VTA GABAergic interneurons = increased dopamine levels
Evolutionary purpose of reward circuit
reinforce survival behaviours like feeding, drinking, sex, maternal/paternal behaviours, social interactions
hijacked by addictive drugs
Nucleus Accumbens
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
Ventral Tegmental Area
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…
Prefrontal Cortex
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
Hippocampus
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
Amygdala
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
Caudate nucleus
voluntary movement, learning, memory, sleep, pain, social behaviour
reciprocal connections with VTA, NAc, hippocampus, and amygdala
where drugs accumulate and bind transporters
Locus coeruleus
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)
Raphe nuclei
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
