T ADDICTED BRAIN NEUROBIOLOGICAL ORMAL ADOLESCENT C …

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THIS LECTURE COVERS INTRODUCTION TO REGIONS & TERMS NORMAL ADOLESCENT BRAIN DEVELOPMENT THE ADDICTED BRAIN NEUROBIOLOGICAL CONSEQUENCES SUMMARY

Transcript of T ADDICTED BRAIN NEUROBIOLOGICAL ORMAL ADOLESCENT C …

THIS LECTURE COVERS

•INTRODUCTION TO REGIONS & TERMS

•NORMAL ADOLESCENT BRAIN DEVELOPMENT

•THE ADDICTED BRAIN

•NEUROBIOLOGICAL CONSEQUENCES

•SUMMARY

NICOTINIC ACETYLCHOLINE RECEPTORS• NICOTINE ACTS ON NACHRS • NACHRS = LIGAND-GATED ION CHANNELS (5 SUBUNITS AROUND AN ION PORE)

• 9 Α-SUBUNITS LABELED FROM Α2 TO Α10 AND 3 Β-SUBUNITS LABELED FROM Β2 TO Β4∙PROMOTE REINFORCING EFFECTS ∙LIMIT REINFORCEMENT ∙MEDIATE AVERSIVE EFFECTS

• IN THE HUMAN BRAIN, THE MOST WIDELY EXPRESSED NACHR IS THE Α4,Β2 SUBUNIT

• REPEATED EXPOSURE 🡪 DESENSITIZATION 🡪 ↑ NUMBER OF NACHRS

• PM=RECEPTORS UNOCCUPIED 🡪 RECOVER TO A RESPONSIVE STATE 🡪 AM =CRAVING AND WITHDRAWAL SX

• SMOKE THROUGHOUT THE DAY TO MAINTAIN PLASMA NICOTINE LEVELS • PREVENT WITHDRAWAL SYMPTOMS • REWARDING EFFECTS FROM THE CONDITIONED REINFORCERS (E.G. SMOKE TASTE & FEEL)

Laviolette & van de Kooy, 2004

NICOTINE - NACHRS• CNS NACHRS REGULATE NT RELEASE

REWARD CIRCUITRY

Ca

rter &

Sw

ard

fage

r, 20

16

Markou, 2008; Watkins et al., 2000

NICOTINE-INDUCED POSITIVE REINFORCEMENT

= drug presentation ↑s probability of a response

Example…Mesolimbic System

Laviolette & van de Kooy, 2004

WITHIN THE VTA…ACUTE

• NIC 🡪 NACHR 🡪 ↑ DA IN VTA• NIC 🡪 NACHR ON GLU TERMINALS 🡪 ↑ DA IN NA & PFC

• NIC 🡪 NACHR ON GABA TERMINALS 🡪 ↓ DA IN NA & PFC

REPEATED EXPOSURE

• GABA NACHRS DESENSITIZE FASTER THAN GLU 🡪 ↑ DA

ADDICTION CYCLEBINGE/INTOXICATIONBasal Ganglia = VS + globus pallidus+ substantia nigra + subthalamic nucleus

WITHDRAWAL/NEGATIVE AFFECTExtended Amygdala = NAc + BNST

PREOCCUPATION/ANTICIPATIONACC + OFC

NEUROTRANSMITTERS(+) HEDONIC EFFECTS…

• DA 🡪 EUPHORIA

• SEROTONIN 🡪 EUPHORIA

• OPIOID PEPTIDES 🡪 EUPHORIA

• GLUTAMATE 🡪 AROUSAL

(-) HEDONIC EFFECTS…• DA 🡪 DYSPHORIA

• SEROTONIN 🡪 DYSPHORIA

• GABA 🡪 ANXIETY, PANIC ATTACKS

• OPIOID PEPTIDES 🡪 PAIN, DYSPHORIA

• NE 🡪 STRESS

• GLUTAMATE 🡪 HYPEREXCITABILITY, MEMORY & LEARNING DEFICITS

• DYNORPHIN 🡪 DYSPHORIA

• CRF 🡪 STRESSKoob & Simon, 2009

NEUROTRANSMITTERS ~ ADDICTION CYCLEBinge/Intoxication Withdrawal/Neg Affect Preoccupation/Anticipation

DA

Opioid

5HT2

GABA

ACh

CRF

Dynorphin

NE

Glutamate

Reward & Incentive Salience

previously neutral stimuli become associated with drug availability🡪 habit formation 🡪 ↑ DA & Glu 🡪 ↑ drug seeking