The prefrontal cortex activity is involved in organizing the short-term memory. Although the involvement of serotonin for an appropriate performance in learning and memory tests is well known, its role is still unclear; as is the cellular basis of short-term memory behavioral performance. Sprague-Dawley rats were stereotactically injected with 1 microg/microl of 5, 7-dihydroxitryptamine to cause a lesion to the dorsal raphe nucleus. Sham-operated or intact rats were also studied as control groups. Before surgery and 20 days post-operatively, each animal was placed in the Biel maze for five consecutive trials. In the pre-treatment test, all three groups decreased significantly the number of errors beginning with the fourth trial. The same occurred in the post-treatment test, except for the experimental group, whose animals committed less errors beginning with the second trial. After behavioral testing, the dorsomedial prefrontal cerebral cortex was dissected out, and the Golgi study of the third-layer pyramidal neurons revealed that the length of both the apical and the basilar dendrites was smaller than that of controls, and that the apical and oblique dendrites had a greater spine density. A major proportion of thin spines was also seen on the basilar and oblique dendrites, and more stubby spines were seen on the apical dendrite. Serotonin depletion in the prefrontal cerebral cortex resulted in cytoarchitectural alterations of the prefrontocortical pyramidal neurons, which may be underlying partially the greater efficiency observed in the short-term memory behavioral performance.