CNR - Institute of Neuroscience CNR
Institute of Neuroscience


Role of genetic factors in drug addiction

Not all individuals who are exposed to drugs of abuse become addicted. Therefore, exposure to drugs of abuse is a condition necessary but not sufficient for addiction to take place in humans.

Genetic epidemiology studies in homo- and heterozygous twins indicates that genetic factors play a fundamental role in the vulnerability to drug addiction.

The study of the role of genetic factors in vulnerability to drug addiction in humans is difficult because obvious ethical and experimental reasons. Therefore, the use of genetic animal models provides a valuable tool to investigate how genetic factors contribute to the increase in drug abuse vulnerability.


The focus of this research project is that of studying differences in mesolimbic DA system functionality in two inbred rat strain (Lewis and Fischer 344 rats) selected for their different vulnerability to drugs of abuse and to stress. According to previous self-administration and conditioned place preference studies Lewis rats appear to be more sensitive, compared to Fischer 344 strain, to the rewarding and motivational effects of different drugs of abuse. To correlate these differences with neurochemical indexes, we investigated by brain microdialysis the acute effect of different drugs of abuse on DA transmission in the nucleus accumbens (NAc) shell and core of these rat strains.

While, depending on the drug and dose used, we found an increased or not different effect on NAc shell DA of Lewis compared to Fischer rats, we consistently found an increased responsiveness of NAc core DA transmission to different drugs of abuse (opiates, psychostimulants, nicotine). This last finding reminds the effect observed in oubred Sprague-Dawley rats sensitized to drugs of abuse. Given the evidences suggesting a role for NAc shell DA in reward and for NAc core DA in incentive motivation these findings would suggest that increased vulnerability of Lewis strain to drugs of abuse might be the result of increased drug rewarding and motivational effect in this strain.

To further elucidate this issue we are investigating the effect of repeated exposure to different drugs of abuse in these strains as well as the neurochemical changes in DA transmission during active (by self-administration) administration of these drugs.


  • Cadoni C, Muto T, Di Chiara G (2009) Nicotine differentially affects dopamine transmission in the nucleus accumbens shell and core of Lewis and Fischer 344 rats. Neuropharmacology 57:496-501.
  • Cadoni C, Di Chiara G (2007) Differences in dopamine responsiveness to drugs of abuse in the nucleus accumbens shell and core of Lewis and Fischer 344 rats. J. Neurochem. 103:487-99.


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Cristina Cadoni

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