Influence of exposure period on in vivo hippocampal glutamate and GABA release in rats chronically exposed to lead

Previous work has demonstrated that continual exposure to 0.2% lead (Pb) be ginning at birth diminishes depolarization-induced hippocampal glutamate (G LU) and GABA release in vivo. The present study sought to extend these find ings by examining Pb-induced changes as a function of exposure period. Rats were continually exposed to 0.2% Pb in the drinking water beginning at con ception (Gestational-Life, GL) or two weeks after weaning (Wean-Life, WL), while exposure in a third group was begun at conception but terminated at w eaning (Gestational-Wean, GW). Hippocampal transmitter release was induced in adult animals by perfusion of 150 mM K+ in the presence of Ca+2 (total r elease) through a microdialysis probe in one test session, followed by perf usion through a contralateral probe in the absence of Ca+2 (Ca+2-independen t release) in the second session. Decreases in total GLU and GABA release w ere observed in the GL and WL groups compared to controls over the first 20 -min after initiation of high K+, decrements that could be attributed to ex posure-induced reductions in Ca+2-dependent release. The pattern of Pb-indu ced changes in the GL group is similar to that observed previously in a gro up continuously exposed from birth, indicating that gestational exposure di d not further enhance the impact of Pb beginning at birth when exposure in both groups extends into adulthood. Similar responses were also found in th e WL group, indicating that exposure during early development is not a requ irement to induce changes in GLU and GABA release. Pb-induced decreases in response were also seen in the GW group: a decrease in Ca+2-dependent GLU r elease was observed, while decrements in total and Ca+2-dependent GABA rele ase were similar to those in the GL and WL groups. Thus, exposure limited t o early development is also sufficient to produce deficits in evoked transm itter release. In addition, the exposure-induced decreases in GLU responses correspond to Pb-induced impairments in long-term potentiation (LTP) obser ved in similarly exposed groups (Gilbert et al., 1999), providing further e vidence that Pb effects on GLU release are a critical factor in the alterat ions found in LTP. (C)1999 Intox Press, Inc.