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

mnorton@rx.uga.edumnorton@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

www.drugabuse.gov