1. Addiction:
Wise: Drug dependence-- cluster of cognitive, behavioral
and physiologic symptoms indicating the person has
impaired control of drug use, and continues to use the
drug despite adverse consequences.
Physical dep.-- adaptive state to the drug, with physical
withdrawal symp.
Psychol dep.-- “pleasure”, high---- pos. reinf.
Neg. reinf.---- drug intake terminates
aversive effects of abstinence
( withdrawal ).
Craving-- memory

2. ADDICTIONS
Wise (1989, 1996): physical vs. psychological dependence
tolerance, withdrawal
Periaqueductal gray (PAG), VTA, n. accumbens,
raphe n., hypoth., amygdala, hippocampus, cingulate,
prefrontal cortex
Endogenous opiates (enkephalin, endorphin) –morphine, opium, heroin (mu, kappa, delta receptors)
DA- cocaine, amphetamine, nicotine, caffeine
Marijuana (THC)- anandamide( “internal bliss”), 2-AG, noladin
ether, virodhamine (4 ligands)
Alcohol - “steady” vs. “binge”, somatization (girls)
Blum et al (1990, 1996); Spear (2000):
Reward deficiency syndrome
Nader et al. (2002)

3. Addicts become accustomed to high levels of dopamine, which plays an important role in the regulation of pleasure. Dopamine is manufactured in nerve cells within the ventral tegmental area and is released in the nucleus accumbens, limbic areas and the frontal cortex.

4. 1. After being released into the synapse, dopamine binds to receptors on the next neuron.
2. Dopamine is either quickly reabsorbed (reuptake) or broken down by the enzyme monoamine oxidase (MAO).

5. Cocaine blocks reuptake of dopamine plus added release
Cocaine blocks reuptake of dopamine plus added release. As a result, dopamine accumulates in the synapse, where it stimulates the receiver cell.

6. Amphetamines stimulate excess release of dopamine, overwhelming the processes of reuptake and enzymatic breakdown.

7. Nicotine stimulates the release of dopamine, while another substance in cigarette smoke blocks the action of MAO.

8. 5-HT – in hypothalamus from raphé n.
Reward-Deficiency-Syndrome(Blum et al., 1996)
ICSS cascade: DA – VTA to n. accumbens, amygdala, hippocampus, septum, cingulate, prefrontal cortex
5-HT – in hypothalamus from raphé n.
Enkephalin – in VTA from hypothalamus, in n. accumbens
GABA – in VTA, n. accumbens
GABAa/BZD - in amygdala
BZD = Benzodiazepine

9. REWARD CASCADE Hypoth VTA N. Accumbens Raphé Amygdala Hippoc
5-HT
ENK
GABA
GABA
ENK
Raphé DA
D1/2 D2
Amygdala DA
Reinforce
Hippoc
GABA
(after Blum et al., 1996)
GABAa (BZD)
P300-wave (EEG) Frontal Cortex
D2 + D4 ???
Anxiety Reduced

10. Spear (2000): Reward-deficiency syndrome in adolescence.
Nader et al. (2002): D2 activity and social status in monkeys.
ICSS & ADDICTION---- Rev.
Olds, Delgado, Deutsch, Stein, Crow, Gallistel,
Gibson et al., Rolls, Shizgal, Wise, Stein & Belluzzi,
Henry, Blum et al., Spear, Nader et al.
Video: Addiction