Effects Of DAMGO And Galantamine On Synaptic Plasticity Of Dentate Gyrus In Lead-exposed Rats

Chronic lead exposure causes a variety of impairments in learning and memoryand cognitive function. And synaptic plasticity in hippocampus is an extensivelystudied cellular model of learning and memory, which includes long-term potentiation(LTP) and long-term depression (LTD) in two forms. Depotentiation (DP) is anotherform of synaptic plasticity. Previous studies show that chronic lead exposure candamage the induction of LTP/LTD in hippocampal CA1 and dentate gyrus (DG) areas.The studies of thesis were carried out of investigate the effects on chronic lead-causedsynaptic plasticity impairment by DAMGO, a selectiveμ-opioid receptor agonists,and we investigated the repair and protection on lead-caused synaptic plasticityimpairment by Galantamine, using field potential recording on chronic lead exposurerats. The methods and results are as follows:Neonatal Wistar rats were exposed to lead from parturition to weaning via milkof dams whose drinking water contained 0.2% lead acetate. Field excitatorypostsynaptic potentials (fEPSPs) in DG area of hippocampus were recorded onpostnatal days 27-30. DAMGO application was followed by an increase in EPSPslopes in both control and lead-exposed rats, while the amplitude of DAMGO-LTP inthe lead-exposed rats was significantly greater than that in controls. DAMGO-LTPcan not be blocked by NMDA receptor antagonist AP5 completely. Chronic leadexposure causes impairment in the amplitude of HFS-LTP, and the impairment wasnot significantly affected by DAMGO treatment, the DAMGO application also didnot influence the amplitude of HFS-LTP in control group. These results indicate thatthe amplitude of DAMGO-LTP in lead-exposured group was greater than controlgroup, and it was depends on the activity of NMDA receptor partly. No significanteffect of DAMGO on HFS-LTP groups is the result of different sites of leadneurotoxicity.Neonatal Wistar rats were exposed to lead from parturition through adulthood bythe drinking of 0.2% lead acetate. Galantamine was applied by intraperitonealinjection every day (1 mg/day/100 g body weight) twoweeks before theelectrophysiological recording. The results showed that chronic lead exposureimpaired LTP/DP induction in DG area of the hippocampus, and Galantamine causeda significant increase on the amplitudes of LTP/DP of lead-exposed rats, but only a small increase in non-exposed group. These results suggest that Galantamine couldreverse the lead-induced impairments of synaptic plasticity in rats and might be aneffective medicine to cure the cognitive deficits induced by lead.By these experiments, we studied the effects on the chronic lead-exposuredimpairments of synaptic plasticity by DAMGO and Galantamine, and possiblemechanisms. All of these findings provided us a more comprehensive understandingabout the toxicity of lead.