CNR - Institute of Neuroscience CNR
Institute of Neuroscience


Sensitization to drugs of abuse: underlying neurochemical changes


The development of drug addiction is characterized by progressively increasing drug use that from casual becomes compulsive. The key question in addiction research is why some individuals undergo a transition from casual to compulsive drug use and why addicted individuals show high rates of relapse.

The transition into addiction is associated with many drug induced changes in the brain and in related psychological functions. Several theories have been formulated to explain how drug induced alterations in brain function might lead to addiction. Among these the incentive sensitization theory supports the notion that sensitization of a neural system (mesolimbic DA system) that attributes incentive salience cause compulsive motivation to take addictive drugs. Sensitization to drugs of abuse is associated with long-lasting changes in key brain structures mediating rewarding and motivational effects of addictive drugs as well as of natural rewarding stimuli.


Given these premises the main focus of this research project is that of elucidating the neurochemical changes in mesolimbic DA transmission induced by repeated exposure to drugs of abuse. By means of in vivo brain microdialysis we have shown that behavioral sensitization to drugs of abuse, induced by repeated drug exposure or by repeated exposure to stressful stimuli, is associated with an increased DA transmission responsiveness in the core and/or a decreased or unchanged responsiveness in the shell of nucleus accumbens. These findings give rise to the question of the significance of this changes in DA transmission in the process of addiction. To the aim of clarifying the role of sensitization in drug addiction we are investigating, by means of self-administration, conditioned place preference (CPP) and conditioned saccharin avoidance (CSA) paradigms combined with brain microdialysis technique, the role of NAc shell and core DA in drugs motivational and rewarding effects.

Microdialysis technique offers an unique opportunity to monitor neurochemical changes simultaneously with observation of operant behavior.


  • Cadoni C, Valentini V, Di Chiara G (2008) Behavioral sensitization to delta 9-tetrahydrocannabinol and cross-sensitization with morphine: differential changes in accumbal shell and core dopamine transmission. J. Neurochem. 106:1586-93.
  • Carta AR, Moreno CC, Cadoni C, Tronci E, Di Chiara G (2008) Long-term increase in GAD67 mRNA expression in the central amygdala of rats sensitized by drugs and stress. Eur. J. Neurosci. 27:1220-30.
  • Di Chiara G, Bassareo V, Fenu S, De Luca MA, Spina L, Cadoni C, Acquas E, Carboni E, Valentini V, Lecca D (2004) Dopamine and drug addiction: the nucleus accumbens shell connection. Neuropharmacology 47 Suppl 1:227-41.
  • Cadoni C, Solinas M, Valentini V, Di Chiara G (2003) Selective psychostimulant sensitization by food restriction: differential changes in accumbens shell and core dopamine. Eur. J. Neurosci. 18:2326-34.
  • Cadoni C, Pisanu A, Solinas M, Acquas E, Di Chiara G (2001) Behavioural sensitization after repeated exposure to Delta 9-tetrahydrocannabinol and cross-sensitization with morphine. Psychopharmacology (Berl.) 158:259-66.
  • Cadoni C, Solinas M, Di Chiara G (2000) Psychostimulant sensitization: differential changes in accumbal shell and core dopamine. Eur. J. Pharmacol. 388:69-76.
  • Cadoni C, Di Chiara G (2000) Differential changes in accumbens shell and core dopamine in behavioral sensitization to nicotine. Eur. J. Pharmacol. 387:R23-5.
  • Cadoni C, Di Chiara G (1999) Reciprocal changes in dopamine responsiveness in the nucleus accumbens shell and core and in the dorsal caudate-putamen in rats sensitized to morphine. Neuroscience 90:447-55.


PI photo

Cristina Cadoni

Contact information

email  E-mail

email  +39 0706758688

Participating staff

Sandro Fenu

Tiziana Muto

Augusta Pisanu

Valentina Valentini