Addicts Those who continue to take a drug despite its negative
effects and efforts to stop
Not the same as physical dependence (motivation
factor is not to prevent withdrawal effects
Withdrawal effects Negative physiological effects of withdrawal
Nearly always opposite effect from drug
Works like tolerance
Physical dependent People who suffer from withdrawal effects when they
stop taking the drug
Mesotelencephalic System of dopaminergic neurons that project from
dopamine system mesencephalon into telencephalon
Neurons have cell body in two midbrain nuclei
(substantia nigra, and ventral tegmental are)
o Neurons with cell body in substantia nigra
project in dorsal striatum (nigrostriatal
pathway)
o Neurons with cell body in ventral tegmental
area project to various cortical and limbic
sites (mesolimbic dopamine system)
release dopamine on receptor of
nucleus accumbens
Axons project also to nucleus accumbens
o Those that project from ventral tegmental
area to nucleus accumbens are involved in
rewarding effects of brain stimulation,
neural reward, and addictive drugs
Proteins and
addiction
- CREB 1. Dopamine signals from dopamine producing cell
of ventral tegmental area (VTA) leads to increase
in cycling AMP and calcium
2. These rises activate CREB
3. CREB bound to DNA and activate specific genes
4. Those genes give rise to proteins involved in
tolerance and dependence
5. E.g. dynorphin, is dispatched to VTA where it
decrease dopamine release and depresses the
reward circuit
6. Causing user to need more drug to feel high
- Delta FosB Key for craving
Stays is body for several month
1. Dopamine signals from VTA leads to
production of protein Delta FosB
2. Represses dynorphin synthesis and activates
certain genes (other than CREB)
3. Genes give rise to proteins involved in
sensitizing responses to drug and to reminders
of past drug use
4. E.g. CDK5 promote structural change that
could make nucleus accumbens neurons
persistently sensitive to drugs and drug
related cues (such as building new dendrites
that connect cells with each other brain
overreact to drug related cues even years later
CREB dominates first, but after a few days it
leaves the body and delta FosB activity and
glutamate signaling predominate
effects and efforts to stop
Not the same as physical dependence (motivation
factor is not to prevent withdrawal effects
Withdrawal effects Negative physiological effects of withdrawal
Nearly always opposite effect from drug
Works like tolerance
Physical dependent People who suffer from withdrawal effects when they
stop taking the drug
Mesotelencephalic System of dopaminergic neurons that project from
dopamine system mesencephalon into telencephalon
Neurons have cell body in two midbrain nuclei
(substantia nigra, and ventral tegmental are)
o Neurons with cell body in substantia nigra
project in dorsal striatum (nigrostriatal
pathway)
o Neurons with cell body in ventral tegmental
area project to various cortical and limbic
sites (mesolimbic dopamine system)
release dopamine on receptor of
nucleus accumbens
Axons project also to nucleus accumbens
o Those that project from ventral tegmental
area to nucleus accumbens are involved in
rewarding effects of brain stimulation,
neural reward, and addictive drugs
Proteins and
addiction
- CREB 1. Dopamine signals from dopamine producing cell
of ventral tegmental area (VTA) leads to increase
in cycling AMP and calcium
2. These rises activate CREB
3. CREB bound to DNA and activate specific genes
4. Those genes give rise to proteins involved in
tolerance and dependence
5. E.g. dynorphin, is dispatched to VTA where it
decrease dopamine release and depresses the
reward circuit
6. Causing user to need more drug to feel high
- Delta FosB Key for craving
Stays is body for several month
1. Dopamine signals from VTA leads to
production of protein Delta FosB
2. Represses dynorphin synthesis and activates
certain genes (other than CREB)
3. Genes give rise to proteins involved in
sensitizing responses to drug and to reminders
of past drug use
4. E.g. CDK5 promote structural change that
could make nucleus accumbens neurons
persistently sensitive to drugs and drug
related cues (such as building new dendrites
that connect cells with each other brain
overreact to drug related cues even years later
CREB dominates first, but after a few days it
leaves the body and delta FosB activity and
glutamate signaling predominate
