It has been reported that cocaine and amphetamine-regulated transcript (Cart) peptides can increase locomotor activity and produce a conditioned place preference. To establish whether or not Cart can be consider as a valuable marker of addiction we performed a comparative study of the expression of Cart and Fos genes by several drugs of abuse. This was achieved using real-time quantitative polymerase chain reaction in four rat brain structures: prefrontal cortex, caudate putamen, nucleus accumbens and hippocampus. As expected, a significant induction of the immediate early gene Fos was observed after acute administration of morphine, cocaine, 3, 4-methylenedioxymethamphetamine and Delta(9)-Tetrahydrocannabinol. On the contrary none of these drugs was able to produce a significant change in Cart mRNA levels demonstrating that the expression of this gene is not modulated by drugs of abuse in these brain structures.