title: Glutamatergic ionotropic blockade within accumbens disrupts working memory and might alter the endocytic machinery in rat accumbens and prefrontal cortex.
abstract: 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 microl injections of saline, (+/-) 2-amino-7-phosphonoheptanoic acid (AP-7) (0.5 or 1 microg) or 2,3-dioxo-6-nitro-1,2,3,4,tetrahydrobenzo-(f)quinoxaline-7-sulphonamide disodium (NBQX, 0.5 or 1 microg) 10 min before testing. An increase by AP-7 was observed in ambulatory movements (0.5 microg; p < 0.05), non-ambulatory movements and number of movements (1 microg; p < 0.05); sniffing and total exploration (1 microg; 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 microg and p < 0.001 for 1 microg). When the second hole was compared with the first of his group, a difference was only observed in the AP-7 1 microg 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.
authors.affiliation: Laboratorio de Neurociencias y Psicología Experimental, Instituto de Medicina y Biología Experimental de Cuyo (IMBECU), Facultad de Ciencias Médicas, Universidad Nacional de Cuyo, Mendoza, Argentina.
authors.forename: G
authors.initials: G
authors.lastname: Baiardi
authors.forename: A M
authors.initials: AM
authors.lastname: Ruiz
authors.forename: A
authors.initials: A
authors.lastname: Beling
authors.forename: J
authors.initials: J
authors.lastname: Borgonovo
authors.forename: G
authors.initials: G
authors.lastname: Martínez
authors.forename: A I
authors.initials: AI
authors.lastname: Landa
authors.forename: M A
authors.initials: MA
authors.lastname: Sosa
authors.forename: P A
authors.initials: PA
authors.lastname: Gargiulo
mesh_terms: D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives / Q000494:pharmacology; D033962:Adaptor Protein Complex 2 / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D004705:Endocytosis / Q000187:drug effects / Q000502:physiology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005973:Glutamine / Q000378:metabolism; D015151:Immunoblotting; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism*; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism*; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors
chemical_list: D033962:Adaptor Protein Complex 2; D018691:Excitatory Amino Acid Antagonists; D011810:Quinoxalines; D016194:Receptors, N-Methyl-D-Aspartate; D005973:Glutamine; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; D015763:2-Amino-5-phosphonovalerate; C031231:2-amino-7-phosphonoheptanoic acid