Glutamatergic ionotropic blockade within accumbens disrupts working memory and might alter the endocytic machinery in rat accumbens and prefrontal cortex.

BAIARDI, G; RUIZ, A. M.; BELING, A.; BORGONOVO, J.; MARTINEZ, G.; LANDA, A.I.; SOSA, M.A.; GARGIULO, P.A.

JOURNAL OF NEURAL TRANSMISSION. GENERAL SECTION.

Springer Verlag

Lugar: Wien; Año: 2007 vol. 114 p. 1519 - 1528

0300-9564

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 ml injections of saline, (±) 2-amino-7-phosphonoheptanoic acid (AP-7) (0.5 or 1 mg) or 2,3-dioxo-6-nitro-1,2,3,4,tetrahydrobenzo-(f)quinoxaline-7- sulphonamide disodium (NBQX, 0.5 or 1 mg) 10min before testing. An increase by AP-7 was observed in ambulatory movements (0.5 mg; p<0.05), non-ambulatory movements and number of movements (1 mg; p<0.05); sniffing and total exploration (1 mg; 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 mg and p<0.001 for 1 mg). When the second hole was compared with the first of his group, a difference was only observed in the AP-7 1 mg 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.