In a first experiment, 14 rats were implanted with an electrode in the ventral tegmental area and trained to self-stimulate. On the experimental day only half of the rats were allowed to self-stimulate for about one hour. All rats were then sacrificed by immersion in liquid nitrogen. Seven brain regions were dissected and assayed for the endogenous concentration of cyclic nucleotides. Self-stimulation induced significant changes in striatum and hippocampus. However, a subsequent experiment showed that the same pattern of changes in the striatum can be produced by motor activity. On the other hand, changes in the hippocampus were specific to the self-stimulation group suggesting that this structure is associated with the brain reward system.