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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.

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Wise drug dependence cluster of cognitive behavioral

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


Wise drug dependence cluster of cognitive behavioral

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)


Wise drug dependence cluster of cognitive behavioral

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.


Wise drug dependence cluster of cognitive behavioral

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).


Wise drug dependence cluster of cognitive behavioral

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


Wise drug dependence cluster of cognitive behavioral

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


Wise drug dependence cluster of cognitive behavioral

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


Wise drug dependence cluster of cognitive behavioral

Reward-Deficiency-Syndrome substance in cigarette smoke blocks the action of MAO.(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


Wise drug dependence cluster of cognitive behavioral

REWARD CASCADE substance in cigarette smoke blocks the action of MAO.

Hypoth VTA N. Accumbens

D2

DA

Reward

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


Wise drug dependence cluster of cognitive behavioral

Spear (2000): Reward-deficiency syndrome in adolescence substance in cigarette smoke blocks the action of MAO..

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