Effects of development and dopamine depletion on striatal NMDA receptor-mediated calcium uptake.
Calcium (Ca(2+)) is the currency of N-methyl-D-aspartate (NMDA) receptor mediated signal transduction pathways involved in the modification of synaptic efficacy during regulation of excitatory inputs into the striatum. The aim of the present study was to investigate the effects of development and dopamine depletion on NMDA receptor function. NMDA receptors were stimulated by incubation of striatal sections (350 microm) in buffer containing NMDA (100 microm) for 2 min, the slices were washed and uptake of radioactively labelled calcium ((45)Ca(2+)) was measured. Dopamine depletion has been reported to result in alterations of glutamate receptor expression and upregulation of NMDA receptor activity. However, the results of the present study show that dopamine depletion does not alter NMDA-stimulated Ca(2+) uptake into rat striatal slices in vitro. Unilateral striatal dopamine depletion was achieved by infusion of 6-hydroxydopamine (6-OHDA, 13.5 microg/4.5 microl) into the medial forebrain bundle (MFB) of the left hemisphere of ten rats. NMDA-stimulated (45)Ca(2+) uptake into striata following dopamine depletion was not significantly different from NMDA-stimulated (45)Ca(2+) uptake into striata obtained from sham-operated rats. Other factors that induce changes in NMDA receptor function include development and aging. In young rats aged 7 weeks old (n = 7) and 16 weeks old (n = 6) a significant 2-3 fold decrease in striatal NMDA receptor function was observed with increasing age over the 9 week period of development. To our knowledge these are the first results to show developmental decreases of NMDA receptor function in the striatum of juvenile rats.
Khoboko
Thabelo
T
Department of Human Biology, Faculty of Health Sciences, University of Cape Town, Anzio Road, Observatory 7925, Cape Town, South Africa. thabelok@email.arizona.edu
Russell
Vivienne A
VA
D000375:Aging / Q000502:physiology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D002118:Calcium / Q000378:metabolism*; D002132:Calcium Radioisotopes; D004298:Dopamine / Q000172:deficiency / Q000502:physiology*; D006892:Hydroxydopamines; D017072:Neostriatum / Q000254:growth & development* / Q000378:metabolism* / Q000473:pathology; D009410:Nerve Degeneration / Q000139:chemically induced / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009434:Neural Pathways / Q000502:physiology; D010300:Parkinson Disease / Q000378:metabolism / Q000473:pathology; D051381:Rats; D020318:Rats, Long-Evans; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D013378:Substantia Nigra / Q000502:physiology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D015854:Up-Regulation / Q000502:physiology
D002132:Calcium Radioisotopes; D006892:Hydroxydopamines; D009419:Nerve Tissue Proteins; D016194:Receptors, N-Methyl-D-Aspartate; D014446:Tyrosine 3-Monooxygenase; D002118:Calcium; D004298:Dopamine