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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
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)
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.
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).
Cocaine blocks reuptake of dopamine plus
added release. As a result, dopamine
accumulates in the synapse, where it
stimulates the receiver cell.
Amphetamines stimulate excess release of
dopamine, overwhelming the processes of
reuptake and enzymatic breakdown.
Nicotine stimulates the release of dopamine,
while another substance in cigarette smoke
blocks the action of MAO.
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
REWARD CASCADE
Hypoth VTA
5-HT
N. Accumbens
D2
DA
ENK
GABA
GABA
Raphé
Reward
ENK
DA
D1/2
Amygdala
D2
DA
Reinforce
Hippoc
GABA
(after Blum et al., 1996)
GABAa (BZD)
P300-wave (EEG)
Frontal Cortex
D2 + D4 ???
Anxiety Reduced
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.
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