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Effects of development and dopamine depletion on striatal NMDA receptor-mediated calcium uptake

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Abstract

Calcium (Ca2+) 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 μm) in buffer containing NMDA (100 μm) for 2 min, the slices were washed and uptake of radioactively labelled calcium (45Ca2+) 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 Ca2+ uptake into rat striatal slices in vitro. Unilateral striatal dopamine depletion was achieved by infusion of 6-hydroxydopamine (6-OHDA, 13.5 μg/4.5 μl) into the medial forebrain bundle (MFB) of the left hemisphere of ten rats. NMDA-stimulated 45Ca2+ uptake into striata following dopamine depletion was not significantly different from NMDA-stimulated 45Ca2+ 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.

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Acknowledgements

This work was supported by the Medical Research Council of South Africa and the University of Cape Town. Thabelo Khoboko was supported by the Levi-Montalcini Fellowship in Neuroscience for African Women awarded by the International Brain Research Organization (IBRO).

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  1. Thabelo Khoboko

    Present address: Division of Neural Systems, Memory and Aging, Arizona Research Laboratories, University of Arizona, Tucson, AZ, USA

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  1. Department of Human Biology, Faculty of Health Sciences, University of Cape Town, Anzio Road, Observatory 7925, Cape Town, South Africa

    Thabelo Khoboko & Vivienne A. Russell

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Correspondence to Vivienne A. Russell.

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Khoboko, T., Russell, V.A. Effects of development and dopamine depletion on striatal NMDA receptor-mediated calcium uptake. Metab Brain Dis 23, 9–30 (2008). https://doi.org/10.1007/s11011-007-9050-9

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