The organophospate dichlorvos (DDVP) is being used as an insecticide as well as in the therapy of cognitive deficits associated with Alzheimer disease in the form of the pro-drug metrifonate (Morris et al. 1998). Both uses depend on its capability to inhibit acetylcholinesterase (AChE) activity. However, a few years ago it has been reported that the enzyme acylpeptide hydrolase (ACPH) displays between 6 to 10 times a higher sensitivity to DDVP compared to AChE (Richards et al. 2000). ACPH catalyzes the hydrolysis of short peptides bearing an acylation in their N-terminal amino acid residue. The biological significance of this enzymatic activity has been elusive. Furthermore, there is a lack of information regarding of DDVP effects upon long-term potentiation (LTP). LTP have been accepted as a model of synaptic plasticity by which learning and memory processes might occur. The aim of our investigation is to test out the hypothesis that DDVP is involved in the enhancement of synaptic plasticity processes through a mechanism that involves ACPH. For these purposes, we studied the effect of acute application of DDVP on the induction of LTP in rat hippocampal slices. Briefly, Sprague-Dawley rats (3-5 weeks old) were sacrificed under anesthesia with halothane, as stated the bioethics protocols of the University of Santiago. Brains were rapidly removed and 400 μm thick slices were obtained using a vibratome. They were kept in gassed (95% CO2, 5% O2) artificial cerebrospinal fluid (ACSF) for at least one hour before recording. Field EPSPs were evoked with electrical stimulation using bipolar electrodes and recorded in the stratum radiatum of the CA1 hippocampal area. LTP was elicited by tetanic stimulation (5 trains, each with 10 bursts at 5 Hz, each burst having 4 pulses at 100 Hz) applied to Schaeffer collaterals. DDVP was applied by injection to the perfusion fluid during 20 min (10 min before and after the stimulation protocol), yielding a final concentration of 50 μM in the recording chamber. Recordings were acquired for 1 h after stimulation. Our results show that the mean of the potentiation achieved in the control condition is 107.9% + 23.3 (S.E.M., n=7), whereas in the slices exposed to DDVP the potentiation reaches a value of 219.1% + 39.9 (S.E.M, n=8); P<0.05 (two-tail, unpaired t-test). Surprisingly, the enzymatic activity of AChE from these slices was not affected by DDVP under the conditions previously described (P=0.673, n=3). Instead ACPH activity was 50% inhibited by DDVP (P<0.0001, n=3). These results support the notion that ACPH is a target of pharmacological and toxicological action of DDVP and suggest a possible role of ACPH in synaptic plasticity processes.