Transcript Dysregulated Postsynaptic Density and Endocytic Zone in the

中國醫藥大學附設醫院
洪崇傑醫師
Stages of drug addiction
Criteria for Substance
Dependence (DSM-IV)
Koob GF and Le Moal M, Science, 1997
Criteria for Substance
Dependence (DSM-V)
 Taking the substance in larger amounts or for longer than the you meant to
 Wanting to cut down or stop using the substance but not managing to
 Spending a lot of time getting, using, or recovering from use of the substance
 Cravings and urges to use the substance
 Not managing to do what you should at work, home or school, because of substance use
 Continuing to use, even when it causes problems in relationships
 Giving up important social, occupational or recreational activities because of substance
use
 Using substances again and again, even when it puts the you in danger
 Continuing to use, even when the you know you have a physical or psychological problem
that could have been caused or made worse by the substance
 Needing more of the substance to get the effect you want (tolerance)
 Development of withdrawal symptoms, which can be relieved by taking more of the
substance.
DSM-V
2~3 symptoms indicate a mild substance use disorder,
4~5 symptoms indicate a moderate substance use disorder,
6 or more symptoms indicate a severe substance use disorder.
“in early remission,” “in sustained remission,” “on
maintenance therapy,” and “in a controlled
environment.”
 Drug-seeking
 Drug-taking behaviors
What happens?
Neural circuitry
Genetics and molecular pathway
A brief summary about
the mechanism underlying
drug addiction
Reward Pathway 自我獎賞系
統
 Natural reward
 Food 食物(美食!)
 Water 水
 Sex 性
 Nurturing 撫摸
 Substance
 所有的酒精跟成癮物質
Neural Circuitry
Mediating the
Activation of GoalDirected Behavior
after rewarding
Stahl’s essential psychopharmacology 5th E.
Stahl’s essential psychopharmacology 5th E.
How abused drugs act as temptation?
Neural Circuitry Mediating Drug Seeking
Repeated psychostimulant or
opioids administration
Prefrontal cortex
 Dysmorphism of pyramidal cells
Nucleus accumbens adpatation
 Promote in presynaptic glutamate release
 Altering postsynaptic responsiveness to released
glutamate
 Enduring change in postsynaptic receptor associated
proteins like PSD-95 and Homer
→dendritic and synaptic change
 Drug dependence is believed to be a result from the
interaction between multiple genetic andenvironmental
factors.
(Imlah 1989; Duaux et al. 2000).
 Opioid receptor, dopamine and COMT
genetic polyphormism well studied
→ lack the NMDA series gene reports in human drug
abusers
Discussion
 Thanks for your attention !