Reparatory effects of nicotine on NMDA receptor-mediated synaptic plasticity in the hippocampal CA1 region of chronically lead-exposed rats.
Activation of neuronal nicotinic acetylcholine receptors (nAChRs) modulates the induction of long-term potentiation (LTP): a possible cellular mechanism of learning. To investigate the effect of nicotine on synaptic plasticity in chronically lead-exposed rats, field excitatory postsynaptic potentials and paired-pulse facilitation (PPF) were recorded in the CA1 area of hippocampal slices from chronically lead-exposed 23-30-day-old rats. The results showed the following. (1) Nicotine (1 microm) facilitated the induction of LTP in CA1 by a weak tetanic stimulation (100 Hz, 20 pulses), which does not by itself produce LTP in lead-exposed rats. This effect was significantly suppressed by mecamylamine, a nicotinic antagonist, suggesting that the facilitation of LTP was through nAChRs. (2) The nicotine-facilitated LTP was blocked by dihydro-beta-erythroidine (DHbetaE), a non-alpha7 nAChR antagonist, whereas long-term depression (LTD) was produced by the combination of nicotine and methyllycaconitine, a alpha7-nAChR antagonist. This type of LTD was blocked by DHbetaE. This suggested that several nAChR subtypes were involved in the nicotine-facilitated synaptic plasticity. (3) Nicotine enhanced PPF in the hippocampal CA1 region, and the nicotine-facilitated LTP in lead-exposed rats was blocked by either d-(-)-2-amino-5-phosphonopentanoic acid, the N-methyl-d-aspartate (NMDA) receptor antagonist, or picrotoxin, an antagonist of gamma-aminobutyric acid(A) receptors. We suggest that nicotine-facilitated synaptic plasticity was due to the activation of NMDARs by disinhibition of pyramidal cells through presynaptic nAChRs. This may represent the cellular basis of nicotine-facilitated cognitive enhancement observed in chronically lead-exposed rats.
Wang
Hui-Li
HL
Department of Neurobiology and Biophysics, School of Life Science and Institute of Polar Environment, University of Science & Technology of China, Hefei, Anhui.
Chen
Xiang-Tao
XT
Luo
Le
L
Lou
Zhi-Yi
ZY
Wang
Shu
S
Chen
Ju-Tao
JT
Wang
Ming
M
Sun
Li-Guang
LG
Ruan
Di-Yun
DY
D000157:Aconitine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D002648:Child; D004079:Dihydro-beta-Erythroidine / Q000494:pharmacology; D005260:Female; D006624:Hippocampus / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology; D006801:Humans; D020263:Lead Poisoning, Nervous System / Q000503:physiopathology*; D017774:Long-Term Potentiation / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009473:Neuronal Plasticity / Q000187:drug effects* / Q000502:physiology; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D018733:Nicotinic Antagonists / Q000494:pharmacology; D010421:Pentanoic Acids / Q000737:chemistry / Q000494:pharmacology; D010852:Picrotoxin / Q000494:pharmacology; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D011978:Receptors, Nicotinic / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
D000157:Aconitine; D000697:Central Nervous System Stimulants; D004079:Dihydro-beta-Erythroidine; D009538:Nicotine; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D010421:Pentanoic Acids; D010852:Picrotoxin; D016194:Receptors, N-Methyl-D-Aspartate; D011978:Receptors, Nicotinic; C054634:methyllycaconitine