ACUTE AND LONGER TERM EFFECTS OF MESO-2,3 DIMERCAPTOSUCCINIC ACID (DMSA) ON THE BEHAVIOR OF LEAD-EXPOSED AND CONTROL MICE

We investigated the effect of chelating agent meso-2,3 dimercaptosucci nic acid (DMSA) on spatial learning and forced-swim immobility in Bing hamton Heterogeneous Stock (HET) mice. Forced-swim immobility (charact erized by increasingly frequent bouts of complete motionlessness in a forced-swim test, i.e., behavioral despair) is reduced by exposure to lead. In Experiment 1, male and female HETs(n = 81)were assigned to le ad-exposed (0.5% lead acetate ad lib in drinking fluid), pair-fed (PF) , or water control groups. Six weeks after the termination of lead exp osure, half of each group was injected intraperitoneally (IF) with 50 mg/kg DMSA or vehicle once per day for 5 days. Following treatment, al l animals were tested for acquisition and extinction in the Morris Wat er maze, followed by immobility testing in an inescapable forced-swim task. Neither Pb nor DMSA affected Morris maze performance. However, c onsistent with previously published work, Pb reduced immobility in the forced-water swim relative to both PF and water controls. Additionall y, lead-exposed males, but not females, showed sustained improvement f ollowing DMSA treatment on immobility measures. Experiment 2 was desig ned to demonstrate the effect of the above DMSA protocol on blood-Pb, and also examined the immediate effects of DMSA on immobility during t reatment. Thus, in Experiment 2, animals were exposed to an identical Pb and DMSA treatment protocol, but the effects of DMSA on immobility during the course of DMSA treatment were measured, and animals were sa crificed immediately after treatment so that blood-Pb measures could b e taken. Under these circumstances, DMSA markedly reversed the lead-in duced reduction in immobility immediately during the treatment phase, Although DMSA clearly reduced blood-lead in males, its influence on fe male blood levels was far less. Taken together, the data from these ex periments suggest that DMSA ameliorates lead-induced immobility change s in mice, but that gender may modulate DMSA's effect on blood-lead an d longer-term behavioral effects. However, further work is needed to c larify the role of gender in response to DMSA.