Changes in the gene expression produced by drugs of abuse differ depending on whether the drug is self-administered by the subject (contingent administration) or injected to the animals by the experimenter (non-contingent administration). To verify whether expression of the opioid peptide precursors and dopamine receptors depend on the direct pharmacological effect of the drug or refl ect the cognitive processes associated with self-administration of morphine we employed “yoked” self-administration procedure. The experiment was performed on C57BL/6J mice that were trained to self-administer morphine. We used the technique of in situ hybridization to measure the dopamine receptors (D1R and D2R) and opioid propeptide (proenkephalin and prodynorphin) mRNA levels in several brain regions implicated in addiction. Differences in the D1R and D2R gene expression were found in the dorsal striatum and nucleus accumbens, where an increase of mRNA levels upon active, but not passive morphine administration was observed. No changes in the expression of both opioid propeptide genes were detected in all investigated brain regions of mice receiving contingent or non-contingent morphine injections. The observed increase in the D1R and D2R genes expression suggests that changes in the dopaminergic system may be specifi cally associated with the motivational and cognitive processes underlying self-administration of morphine. Supported by EU grants: LSHM-CT-2007-037669 and LSHM-CT-2004-005166.