NMDA-mediated modulation of dopamine release is modified in rat prefrontal cortex and nucleus accumbens after chronic nicotine treatment |
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Authors: | Massimo Grilli,Anna Pittaluga&dagger ,Emilio Merlo-Pich&Dagger , Mario Marchi&dagger |
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Affiliation: | Department of Experimental Medicine, Section of Pharmacology and Toxicology, University of Genoa, Genoa Italy; Center of Excellence for Biomedical Research, University of Genoa, Genoa Italy; GlaxoSmithKline S.p.A., Medicines Research Centre, Verona, Italy |
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Abstract: | In this study, we investigate the effects of chronic administration of (−)nicotine on the function of the NMDA-mediated modulation of [3H]dopamine (DA) release in rat prefrontal cortex (PFC) and nucleus accumbens (NAc). In the PFC synaptosomes NMDA in a concentration-dependent manner evoked [3H]DA release in rats chronically treated with vehicle (14 days) with an EC50 of 13.1 ± 2.0 μM. The NMDA-evoked overflow of the [3H]DA in PFC nerve endings of rats treated with (−)nicotine was significantly lower (−43%) than in vehicle treated rats. The EC50 was 9.0 ± 1.4 μM. Exposure of NAc synaptosomes of rats treated with vehicle to NMDA produced an increase in [3H]DA overflow with an EC50 of 14.5 ± 5.5 μM. This effect was significantly enhanced in chronically treated animals. The EC50 was 10.5 ± 0.5 μM. The K+-evoked release of [3H]DA was not modified by the (−)nicotine administration. Both the changes of the NMDA-evoked [3H]DA overflow in the NAc and PFC disappeared after 14 days withdrawal. The results show that chronic (−)nicotine differentially affects the NMDA-mediated [3H]DA release in the PFC and NAc of the rat. |
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Keywords: | [3H]dopamine release chronic (−)nicotine treatment isolated nerve endings nucleus accumbens prefrontal cortex pre-synaptic NMDA receptors |
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