Glutamatergic ionotropic blockade within accumbens disrupts working memory and might alter the endocytic machinery in rat accumbens and prefrontal cortex
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- 作者：G. Baiardi ; A. M. Ruiz ; A. Beling ; J. Borgonovo ; G. Martínez ; A. I. Landa ; M. A. Sosa and P. A. Gargiulo
- 关键词：Keywords ; NMDA ; glutamatergic transmission ; nucleus accumbens ; anxiety ; hole board ; schizophrenia ; working memory ; perception
- 刊名：Journal of Neural Transmission
- 出版年：2007
- 出版时间：December, 2007
- 年：2007
- 卷：114
- 期：12
- 页码：1519-1528
- 全文大小：203.4 KB
- 刊物类别：Medicine
- 刊物主题：Medicine & Public Health
Neurology
Pharmacology and Toxicology
Psychiatry - 出版者：Springer Wien
- ISSN：1435-1463
文摘
Effects of blocking N-methyl-D-aspartic acid (NMDA) and non-NMDA glutamatergic receptors on performance in the hole board test was studied in male rats bilaterally cannulated into the nucleus accumbens (Acc). Rats, divided into 5 groups, received either 1?μl injections of saline, (±) 2-amino-7-phosphonoheptanoic acid (AP-7) (0.5 or 1?μg) or 2,3-dioxo-6-nitro-1,2,3,4,tetrahydrobenzo-(f)quinoxaline-7-sulphonamide disodium (NBQX, 0.5 or 1?μg) 10?min before testing. An increase by AP-7 was observed in ambulatory movements (0.5?μg; p < 0.05), non-ambulatory movements and number of movements (1?μg; p < 0.05); sniffing and total exploration (1?μg; p < 0.01). When holes were considered in order from the first to the fifth by the number of explorations, the most visited holes (first and second) of the AP-7 group were significantly higher than the corresponding holes of saline group (p < 0.05 for 0.5?μg and p < 0.001 for 1?μg). When the second hole was compared with the first of his group, a difference was only observed in the AP-7 1?μg group (p < 0.001). Increasing differences between the other holes and the first were observed by drug treatment. At molecular level, it was observed that AP-7 induced an increase of the coat protein AP-2 expression in Acc, but not AP-180 neither the synaptic protein synaptophysin. The increase of AP-2 was also observed in the medial prefrontal cortex by the action of AP-7 but not NBQX. We conclude that NMDA glutamatergic blockade might induce an activation of the endocytic machinery into the Acc, leading to stereotypies and perseverations, lacking cortical intentional direction.