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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.
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
Psychol dep.-- “pleasure”, high---- pos. reinf.
Neg. reinf.---- drug intake terminates
aversive effects of abstinence
( withdrawal ).
Wise (1989, 1996): physical vs. psychological dependence
Periaqueductal gray (PAG), VTA, n. accumbens,
raphe n., hypoth., amygdala, hippocampus, cingulate,
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.
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
Hypoth VTA N. Accumbens
(after Blum et al., 1996)
P300-wave (EEG) Frontal Cortex
D2 + D4 ???
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.