Journal
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
Volume 379, Issue 1, Pages 37-45Publisher
SPRINGER
DOI: 10.1007/s00210-008-0344-1
Keywords
Carbachol; Hippocampus; Lead; Learning and memory; Muscarinic receptor
Categories
Funding
- National Basic Research Program of China [2002CB512907]
- National Nature Science Foundation of China [30630057, 30670554, 30670662, 30672290]
- Academia Sinica [KZCX3-SW-437]
- China Postdoctoral Science Foundation [20060400719]
- K.C. Wong Education Foundation of Hong Kong
- Anhui High Education Natural Science Program [ZD2008010-2]
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The cholinergic system is believed to be associated with learning and memory functions. Lead (Pb2+) is a well-known neurotoxic metal that causes irreversible damage to the central nervous system (CNS). To investigate whether Pb2+ interferes with cholinergic modulation, we examined the effects of carbachol (CCh), a muscarinic cholinergic agonist, on synaptic transmission and plasticity in the CA1 area of the hippocampus of developmentally Pb2+-exposed rats. The results showed that: (1) In both control and Pb2+-exposed rats, 0.1 mu M CCh significantly enhanced tetanus-induced long-term potentiation (LTP), while 5 mu M CCh induced a reversible depression of field excitatory postsynaptic potentials (fEPSPs). However, both the enhancement of LTP and depression of fEPSPs were significantly smaller in Pb2+-exposed rats than in controls, suggesting that the extent of the effect of CCh on the cholinergic system was depressed by Pb2+. (2) In Pb2+-exposed rats, the enhancement of LTP induced by 0.1 mu M CCh was attenuated by pirenzepine, a M(1)AChR antagonist, but was not affected by methoctramine tetrahydrochloride (M-105), a M(2/4)AChR antagonist. The depression of fEPSPs induced by 5 mu M CCh was reduced by either pirenzepine or M-105. (3) Furthermore, paired-pulse facilitation (PPF) was not affected by 0.1 mu M CCh in control and Pb2+-exposed rats but was increased by 5 mu M CCh in either group; the increase in PPF was less pronounced in Pb2+-treated when compared to control rats. These results suggested that cholinergic modulation could be impaired by Pb2+, and this kind of impairment might occur via different mAChR subtypes. Our study delineated the effects of Pb2+ on muscarinic modulation, and this might be one of the underlying mechanisms by which Pb2+ impairs learning and memory.
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