T ADDICTED BRAIN NEUROBIOLOGICAL ORMAL ADOLESCENT C …
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)
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