Yeni Symposium Dergisi

Until recently, many researchers have focused on the role of dopamine in the process of drug ad-diction. What makes dopamine so popular is the ability of addicted substance to increase the brain dopamine concentrations in the limbic regions of the brain. The reinforcing effect of dopamine ma-kes it number one suspected neurotransmitter in

the area of addiction research. However, the incre-ase in the dopamine per se is insufficient to account the process of addiction, since drugs of abuse incre-ase dopamine in naïve as well as addicted subjects. The magnitude of drug-induced dopamine

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Ali Saffet Gönül

Assoc. Prof. of Psychiatry, Ege University School of Medicine Department of Psychiatry, ‹zmir

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SY M P O S I U

yeni MYeni Symposium 42 (3): 00-00, 2004 139 Substance

Figure 1: Schematic description of impaired response inhibition and salience attribution

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Loss of inhibitory function over amygdala REWARD Cue conditioning process including amygdala and hippocampus Disinhibition df sensory driven affective responses

SHORT-TERM EFFECTS OF ADDICTED SUBSTANCES

LONG-TERM EFFECTS OF ADDICTED SUBSTANCES

Cues related to substance or stress Amygdala activation Conditioned response (substance taking)

Dysphoria _{capacity of prefrontal}Loss of funtional cortex over amygdala

Loss of self directed and willed behaviors

S Y M P O S I U

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Yeni Symposium 42 (3): 139-140, 2004 _M

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ases, and intensity of self-reports of the drug’s rein-forcing properties appear to be smaller in the ad-dicted than in naïve patients. This difference can not be attributed solely on receptor changes. It has been recently shown that self administration of co-caine, but not food, results in morphological chan-ges in dentrites and dentritic spines in the prefron-tal cortex and nucleus accumbens. In structural vo-lumetric studies volume losses in the prefrontal cortex has been reported in heroin, alcohol and co-caine-dependent substance. Thus dopamine and re-lated mechanisms in the addiction process, causes changes in the prefrontal cortex.

It is very interesting that dopamine controls the medial frontal cortex which has a very important function of suppressing amygdala. Indeed, during intoxication losing of inhibition over amygdala re-leases behaviors that are normally kept under close monitoring. In the long-term substance via dopami-nergic and other related mechanisms disturb the cellular structure and functional capacity of pref-rontal cortex and resulted in attenuation of the re-levance of motivational, higher cognitive, and self-monitoring functions. It is later understood that not only with substance intake but also during cra-ving and anticipation of a future drug reward in the addicted patients, this process is going on.

It is proposed that behaviors and associated mo-tivational states that are the core of the addiction are distinctly processes of loss of self-directed and willed behaviors to automatic sensory-driven for-mulas and attribution of primary salience to the drug of abuse at the expense of other available re-warding stimuli. With the rere-warding effect addic-ted substance become cue conditioned and turn out to be a chronic tendency. With the loss of pref-rontal cortex control over amygdala, this conditi-oned response takes palace with every cue. Thus, Goldstein and Volkow conceptualized drug addicti-on syndrome as syndrome of “impaired respaddicti-onse inhibition and salience attribution”.

REFERENCES

Goldstein RZ, Volkow ND (2002) Drug addiction and its un-derlying neurobiological basis: neuroimaging evidence for the involvement of the frontal cortex. Am J Psychi-atry; 159: 1642-1652.

Lindsey KP, Gatley SJ, Volkow ND (2003) Neuroimaging in drug abuse.

Curr Psychiatry Rep; 5: 355-361.

Volkow ND, Fowler JS, Wang GJ (2002) Role of dopamine in drug reinforcement and addiction in humans: results from imaging studies. Behav Pharmacol; 13: 355-366. Volkow ND, Fowler JS, Wang GJ (2003) The addicted human

brain: insights from imaging studies. J Clin Invest; 111: 1444-1451.