Effects of acute amphetamine administration on AMPA-mediated synaptic activity and expression of AMPA receptor subunit 2 of brain neurons.
We investigated the role of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor (AMPAR) in mechanisms underlying the action of amphetamine (Amph) on brain neurons, for AMPAR has been proposed to participate in psychotic and neurodegenerative disorders. In the cultured rat brain cortical neurons pretreated with 1 microM Amph for 1 h, the accumulation of 45Ca2+ driven by 10 min incubation with 100 microM AMPA was reduced by about 36%. This Amph-induced decrease seems to involve L-type voltage-gated Ca2+ channels, because the AMPA-induced 45Ca2+ uptake was blocked by 70% and 80%, respectively, for untreated and Amph-treated neurons in the presence of nifedipine (1 microM), an antagonist to L-type calcium channels. Whole-cell, patch-clamp recording revealed that AMPA-elicited current amplitude became 26% lower than the control in Amph-treated cultured neurons. Moreover, Amph treatment down-regulated the level of flip-form glutamate receptor 2 (GluR2) mRNA by 27% in cultured neurons but did not change the expression of GluR2 proteins and flop-form mRNA, as detected by quantitative immunocytochemistry and in situ hybridization. In contrast, in postnatal day 4 rats at 1 h after receiving one intraperitoneal injection of 5 mg/kg of Amph, levels of flip GluR2 mRNA were up-regulated by 13% and 18% in neurons of motor cortex layer 5 and pyramidal neurons of hippocampal CA3, respectively. The data suggest that acute action of Amph on brain neurons is possibly associated with decreased AMPA-mediated Ca2+ influx and current amplitude, as well as modified expression of the GluR2 mRNA.
Yu
Meng-Fen
MF
Chang Gang Institute of Technology, School of Nursing, Tao-Yuan, Taiwan, ROC.
Chien
Chung-Liang
CL
Lee
Wang-Tso
WT
Yin
Hsiang-Shu
HS
D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002132:Calcium Radioisotopes; D002478:Cells, Cultured; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D018408:Patch-Clamp Techniques; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D018091:Receptors, AMPA / Q000235:genetics* / Q000378:metabolism; D013566:Sympathomimetics / Q000494:pharmacology*; D013569:Synapses / Q000502:physiology; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
D002132:Calcium Radioisotopes; D018690:Excitatory Amino Acid Agonists; D012333:RNA, Messenger; D018091:Receptors, AMPA; D013566:Sympathomimetics; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D000661:Amphetamine; C104722:glutamate receptor ionotropic, AMPA 2; D002118:Calcium