The dopamine reward pathway is an evolutionarily conserved brain structure that has a role in processing primary biological rewards such as food, reproduction, social interactions and creating perception of pleasure. Short-term stimulation with psychostimulants retains dopamine in the synaptic cleft and disrupts homeostatic mechanisms, which impairs normal function of the dopamine system. Long-term stimulation promotes longlasting changes at the molecular level, including changes in gene expression and neuronal function and morphology. Neural plasticity is a process of neuronal reorganization that occurs as a consequence of a long-term stimulation of dopamine receptors. Changes that occur during chronic exposure to psychostimulants are decreased expression of D2 dopamine receptors and transporters as well as changes in the biochemical composition of neurons. Those changes can be monitored and measured by experimental methods such as conditioned place preference, self-administration and behavioral senzitization. Transcriptional factors CREB (cAMP response element binding protein) and ΔFosB (DeltaFosB) play a role in functional plasticity and mediate tolerance and senzitization related to increased drug self-administration. By reducing dopamine transmission to the NAc (nucleus accumbens), CREB reduces senzitization and promotes drug self-administration by negative reinforcement. Activation of ΔFosB enhances senzitization and promotes self-administration of drugs and primary rewards by postitive reinforcement. Neurotrophic factors, such as BDNF (brain-derived neurotrophic factor), but also small non-coding miRNA (micro ribonucleic acid) play a role in morphological plasticity. miRNA-212 has also been shown to influence the production of neurotrophic factors and signalization of cAMP, that indirectly regulates cocaine administration.