کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2533031 1559040 2011 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Clozapine and N-Methyl-d-Aspartate have positive modulatory actions on their respective discriminative stimulus properties in C57BL/6 mice
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب سلولی و مولکولی
پیش نمایش صفحه اول مقاله
Clozapine and N-Methyl-d-Aspartate have positive modulatory actions on their respective discriminative stimulus properties in C57BL/6 mice
چکیده انگلیسی

The impairment of N-Methyl-d-Aspartate receptors is thought to contribute to negative symptoms and cognitive deficits. In vitro studies suggest that atypical antipsychotic drugs like clozapine may help to alleviate these deficits by enhancing glutamatergic function. The present study examined the in vivo interaction of clozapine with N-Methyl d-aspartate by training one group of C57BL/6 mice to discrimination 2.5 mg/kg clozapine from vehicle and another group to discriminate 30 mg/kg N-Methyl d-aspartate from vehicle in a two-lever drug discrimination task. Cross-generalization testing revealed that N-Methyl d-aspartate (3–56 mg/kg) failed to substitute for clozapine in the clozapine-trained mice, while clozapine (0.625 mg/kg) produced partial substitution in the N-Methyl d-aspartate-trained mice. Interestingly, administration of a low, non-generalizing dose of each training drug in combination with the full range of doses of the alternate training drug produced full and dose–dependent substitution in both clozapine- and N-Methyl d-aspartate-trained mice. The α1 antagonist prazosin fully and dose-dependently substituted for both clozapine and N-Methyl d-aspartate. These results suggest that the shared discriminative stimulus properties between clozapine and N-Methyl d-aspartate may be mediated through indirect mechanisms, possibly in part through α1 adrenergic antagonism.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: European Journal of Pharmacology - Volume 650, Issues 2–3, 15 January 2011, Pages 579–585
نویسندگان
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