What’s Up-The Neurobiology of What’s Up-The Neurobiology of Learning and Adolescent Substance Learning and Adolescent Substance
AbuseAbuse
Merrill Norton Pharm.D.,D. Ph., NCAC II, CCSMerrill Norton Pharm.D.,D. Ph., NCAC II, CCS
Clinical Associate ProfessorClinical Associate Professor
University of GeorgiaUniversity of Georgia
College of PharmacyCollege of Pharmacy
Athens,Georgia 30602Athens,Georgia 30602
706-542-5371706-542-5371
[email protected]@rx.uga.edu
Neurobiology and Behavior
How are human behaviors and neurobiology related?
LearningLearning
““......relatively permanent changes in behavior relatively permanent changes in behavior produced by experienceproduced by experience””– Learning involves changes in the nervous Learning involves changes in the nervous
system produced by experiencessystem produced by experiences– Nervous system changes are physicalNervous system changes are physical– Learning allows us to adapt our behaviors to Learning allows us to adapt our behaviors to
the environment the environment – Learning involves interactions among the Learning involves interactions among the
motor, sensory, and memory systemsmotor, sensory, and memory systems
14.3
Forms of LearningForms of Learning
PerceptualPerceptual learning functions to identify objects learning functions to identify objects and situationsand situations
Stimulus-ResponseStimulus-Response learning involves making a learning involves making a response when a particular stimulus is presentresponse when a particular stimulus is present– Classical conditioningClassical conditioning– Operant ConditioningOperant Conditioning
MotorMotor learning involves forming new circuits in learning involves forming new circuits in motor systemmotor system
Relational Relational learning involves identifying learning involves identifying connections between stimuliconnections between stimuli
14.4
Overview of LearningOverview of Learning
14.5
Relational LearningRelational Learning Relational learningRelational learning involves connections between involves connections between
individual stimuliindividual stimuli Examples of relational learning includeExamples of relational learning include
– Forming an association between the image of an Forming an association between the image of an object and the sounds of that objectobject and the sounds of that object
– Knowing the content of a space and the relationship Knowing the content of a space and the relationship between the objects in that space (between the objects in that space (spatial learningspatial learning))
– Remembering sequences of events (Remembering sequences of events (episodic learningepisodic learning))– Viewing and recalling the actions of another person Viewing and recalling the actions of another person
((observational learningobservational learning))
14.6
The Hebb RuleThe Hebb Rule Donald Hebb argued that synapses that are Donald Hebb argued that synapses that are
active at the same time that the postsynaptic active at the same time that the postsynaptic neuron fires, are strengthened over timeneuron fires, are strengthened over time– Implies that repeated neural activity will produce Implies that repeated neural activity will produce
physical changes in the nervous systemphysical changes in the nervous system Rats exposed to enriched environments Rats exposed to enriched environments
exhibit neural changes:exhibit neural changes:– Thicker cortexThicker cortex– More glial cellsMore glial cells– More Acetylcholine(Long term Memory)More Acetylcholine(Long term Memory)
14.7
Neurobiological Foundations Neurobiological Foundations of Mental Health and Illnessof Mental Health and Illness
(Modified from Andreasen and Black, 2001)(Modified from Andreasen and Black, 2001)
Thoughts, Feelings, and BehaviorThoughts, Feelings, and Behavior
MindMind//BrainBrain SystemsSystems (mental/cognitive systems such as emotion or (mental/cognitive systems such as emotion or
language, chemical systems such as dopamine or serotonin).language, chemical systems such as dopamine or serotonin).
CircuitsCircuits
CellsCells
MembranesMembranes
MoleculesMolecules
GenesGenes
Limbic Cortex and Limbic Cortex and HypothalamusHypothalamus
• Planning• Attention• Judgment• Reflection• Prioritizing• Self control• Strategizing• Sequencing• Anticipation• Organization• Impulse control• Second thought• Working memory• Modulating mood• Response flexibility• Goal-directed behavior• Foresee consequences
Brain CEO: Frontal Cortex
The “Oops” Center–anterior cingulate gyrus
• The cingulate is responsible for helping focus attention
• Links cingulate and emotional hippocampus for integrating reason & emotion to guide decisions
• May involve ability to empathize
• Undergoes high myelination (doubles) during adolescence
• “Oops center” anticipates risk, detects and keeps us from making errors
Myelin DevelopmentMyelin Development
Developmental Model of Psychopathology
2 4-5 6-7 12 14 21
0
Autism SchizoidReactiveAttachmentSeparationAnxiety
ODDConductDisorder
TourettesPDDMentalRetardationAnxiety
ODDADHDSeparationAnxietyOveranxious
ConductDisorderAbuse/Dependence
EatingDisorderSchizophreniaDepressionAbuse/Dependence
EatingDisorderIdentityDisorderAbuse/Dependence
6MOS
Mood Chart of the Human Brain
Mania
Euphoria
Normal
Sadness
Depression
Homeostasis
How Drugs WorkHow Drugs Work
Interact with neurochemistryInteract with neurochemistry
Results:Results:
- Feel Good – Euphoria/reward- Feel Good – Euphoria/reward
- Feel Better – Reduce negative - Feel Better – Reduce negative feelingsfeelings
Dopamine Spells REWARDDopamine Spells REWARD
Release
Activate
Recycle
What memories do you associate with this image?
visual-colour -shape
smell
emotionsauditory
taste
language
Basal Ganglia- “The Basal Ganglia- “The Secretary”Secretary”
Limbic System- “The Driver”Limbic System- “The Driver”
Brain Development/AgingBrain Development/Aging
Recent research(imaging studies) have Recent research(imaging studies) have given scientists an estimate of brain given scientists an estimate of brain chemistry development:chemistry development:
Age 11 - 50% complete (pre-puberty)Age 11 - 50% complete (pre-puberty) Age 18 - 75% complete(post puberty)Age 18 - 75% complete(post puberty) Age 24-34 - 100% completeAge 24-34 - 100% complete Age 44 - 75% Age 44 - 75% Age 60 - 50%Age 60 - 50%
Addiction Risk FactorsAddiction Risk Factors
GeneticsGenetics Young Age of OnsetYoung Age of Onset Childhood Trauma (violent, sexual)Childhood Trauma (violent, sexual) Learning Disorders (ADD/ADHD)Learning Disorders (ADD/ADHD) Mental IllnessMental Illness
– DepressionDepression– Bipolar DisorderBipolar Disorder– PsychosisPsychosis
Diagam_Brain Normal C.Diagam_Brain Normal C.Diagam_Brain Normal C.
Cortex
HICC Hypothalamic Instinctual Control Centers
Midbrain
Personality & Perception
1
2
3
PlanningInhibitionsSensorium
Thinking Brain
6 F’SFood Intake FeelingsFluid Intake FightFlirtations Flight
“Rational Animals
NORMAL BRAIN
NORMAL BRAIN FUNCTIONS Diagam_Brain Normal C.
““The Necessary Nine”The Necessary Nine” Norepinephrine/Epinephrine-Norepinephrine/Epinephrine-
stimulant,anger,fear,anxiety,fight,flightstimulant,anger,fear,anxiety,fight,flight SerotoninSerotonin-depressant,sleep,calm,pleasure-depressant,sleep,calm,pleasure GABAGABA-relaxant,stress reduction,seizure threshold-relaxant,stress reduction,seizure threshold EndorphinsEndorphins-pain relief,pleasure-pain relief,pleasure AcetylcholineAcetylcholine-involutary actions,memory,motivation-involutary actions,memory,motivation AnandamideAnandamide-memory,new learning,calmness-memory,new learning,calmness GlutamateGlutamate-organization of brain -organization of brain
signaling,memory,painsignaling,memory,pain DopamineDopamine-perception,movement,pleasure-perception,movement,pleasure PIPPIP- loving of one’s self,others,GOD- loving of one’s self,others,GOD
Alcohol
Benzodiazepines
Valium
Xanax
Ativan
Non benzodiazepine
Ambien
Sonata
Barbiturates
Fiorinal
Soma
Cocaine
Amphetamine
Methamphetamine
Ephedrine
Ritalin
Ecstasy
Mescaline
DOM
LSD
Psilocibin
DMT
Ibogaine
PCP
Ketamine
Opioids
Opiates
Heroin
Buprenex
Oxycontin
Nicotine
Marijuana
GABA norepinephrineserotonin cannabinoid
opiateNMDA
acetylcholine
GHB
Thinking Brain
Judgment Brain
Instinctual Brain
Pleasure Brain
“I want a beer”
“It makes me feel goooood”
“Miller Lite”
Neurotransmitters of Dependence
PIPDopamineGlutamate
AcetylcholineAnandamide
Endorphins / EnkelphinsGABA
SerotoninEpinephrine / Norepinephrine
Dependence Recovery
Depletion may take less than 12
months
Replenishment may take 5 to 7 years
Alcohol and the Adolescent Brain
Alcohol 25 yrsAlcohol 25 yrsCocaine 2 yrsCocaine 2 yrs
Marijuana 12 Marijuana 12 yrsyrs
NormalNormal
SPECT SCANSSPECT SCANS
Endorphins
The Hijacking of the Brain and the HPA Axis
Cortisol
Exercise,Food,Psychoactive Chemicals
Psychoactive ChemicalsPsychoactive Chemicals
AlcoholAlcohol Ecstasy/MethamphetamineEcstasy/Methamphetamine MarijuanaMarijuana
Alcohol as a Reinforcer: Neural Alcohol as a Reinforcer: Neural SystemsSystems
Activation of mesocorticolimbic system
The Secretary
The Driver
MethamphetamineMethamphetamine
MethamphetamineMethamphetamine
Before and AfterBefore and After
Is Marijuana Addicting?Is Marijuana Addicting?
The Brain’s Marijuana Receptor The Brain’s Marijuana Receptor SitesSites
The “Secretary”
“Fight or Flight”
Coordination
Brain Cannabinoid ReceptorsBrain Cannabinoid Receptors
Basal GangliaBasal Ganglia– Unconscious muscle movementsUnconscious muscle movements
Limbic SystemLimbic System– HippocampusHippocampus
Short term memory processed into long term memoryShort term memory processed into long term memory
– AmygdalaAmygdala Controls rage, lust, fear and other strong emotionsControls rage, lust, fear and other strong emotions
– CerebellumCerebellum Balance and planning of movementBalance and planning of movement
AnandamideAnandamide
Sanskrit ananda means “bliss”Sanskrit ananda means “bliss” Chemical messenger involved in mood, Chemical messenger involved in mood,
memory, pain perception and appetitememory, pain perception and appetite Natural molecular keyNatural molecular key THC fits same receptorTHC fits same receptor Anandamide is fragile and breaks down Anandamide is fragile and breaks down
quicklyquickly– No intense high like THCNo intense high like THC
ChocolateChocolate
MJ use Lowers Glucose MJ use Lowers Glucose Metabolism in Frontal and Metabolism in Frontal and
Temporal LobesTemporal Lobes
P. hipp.
Medial OFC
Superior
Middle
Inferior
Temporal Gyri
Marijuana Makes People Stupid…
and they stay stupid..
Multiple Neurotransmitter Receptor Sites For Marijuana
Anandamide
GABADopamine
Glutamate
The Blood-Brain Barrier
THC Binds To Glial Cells of BBB
The learned helplessness that results from exposure to the absence of control generalizes to other situations. Marijuana creates the state of learned helplessness.
PSYCHOACTIVE CHEMICAL DEPENDENCE IS A PSYCHOACTIVE CHEMICAL DEPENDENCE IS A COMPLEX ILLNESSCOMPLEX ILLNESS
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