The antisense DNA method has been used successfully to block th expres
sion of specific genes in vivo in neuronal systems. An increasing numb
er of studies in the last few years have shown that antisense DNA admi
nistered directly into the brain can modify various kinds of behaviors
. These findings strongly suggest that the;antisense DNA method can be
used as a powerful tool to study causal relationships between molecul
ar processes in the brain and behavior In this article we review the c
urrent status of the antisense method in behavioral studies and discus
s its potentials and problems by focusing on the following four aspect
s: (i) optimal application paradigms of antisense DNA methods in behav
ioral studies; (ii) efficiencies of different administration methods o
f antisense DNA used in behavioral studies; (iii) determination of spe
cificity of behavioral effects of antisense DNA; and (iv) discrepancie
s between antisense DNA effects on behaviors and those on protein leve
ls of the targeted gene.