This study examined whether depletion of central norepinephrine produces an improved retrieval of aversive memories in the same way as pre-exposure to inescapable footshocks, in rats. Animals conditioned in a T-maze with appetitive (10% sucrose) and aversive (2.0 mA footshock) events were given a single dose of DSP-4 (100, 200 or 400 micrograms/rat) or drug vehicle ICV 24 hr later. The retention performance and activity were assessed 48 hr after the treatment with this neurotoxin. DSP-4 had no effect on open field activities but enhanced latencies to enter both, previously shocked and appetitively reinforced, goalboxes. The data thus, suggest that central administration of DSP-4 does not result in selective enhanced aversive memories. On the contrary, post-trial NE depletion with this neurotoxin might interfere with the retrieval of previously learned association with appetitive stimuli. DSP-4 significantly reduced monoamines, depending upon the brain regions assayed and the doses studied. However, only decreased NE in striatum coincided with the memory changes suggesting that NE innervation to striatum may participate in the retrieval process.