Sedative-like effect of intraperitoneal GABA administration in the open field test

Gamma-Amino Butyric Acid (GABA) is the main inhibitor neurotransmitter of the Central Nervous System (CNS). Its peripheral administration has been matter of discussion. On the one hand, it has been reported that it does not cross the Blood-Brain Barrier (BBB), and, on the other hand, it has been associated with multiple therapeutic regimens and supplements by peripheral administration. The aim of the present study is to elucidate the possibility of a central sedative effect when administered peripherally. An experimental cohort of 90-day-old Holtzman male rats weighing 240-270 g was used. It was divided into 2 groups: saline-controls (n = 9) and GABA treated rats (12.5 mg/kg, n = 9). Both groups were intraperitoneally injected. The motor behavioral patterns displayed in the Opto Varimex (OVM) were studied. Vertical, horizontal, ambulatory and non-ambulatory movements and the number of movements were recorded in an automated way. Horizontal movements constitute the integration of ambulatory and non-ambulatory movements. Student t test was used comparing groups. In this experiment, there were non-significant downward trends in vertical, ambulatory, non-ambulatory and number of movements. Ambulatory and non-ambulatory tendencies acquired significance when treated together as horizontal movements (p < 0.05). We may conclude that peripheral administration of GABA produced a decrease of the horizontal movements in the open field test. It may be interpreted as a sedative effect, suggesting a passage of GABA through BBB, with central effects. However, there are several alternative possibilities to explain present findings. Other experiments will elucidate the implications or scope of the present findings.Fil: Gargiulo, Augusto Pascual Ítalo. Laboratorio de Neurociencias y Psicología Experimental; Argentina. Universidad Católica de Cuyo - Sede San Juan. Facultad de Ciencias Médicas; ArgentinaFil: Marquez Herrero, Santiago. Laboratorio de Neurociencias y Psicología Experimental; Argentina. Universidad Católica de Cuyo - Sede San Juan. Facultad de Ciencias Médicas; ArgentinaFil: Romanowicz, Esteban Alejandro. Laboratorio de Neurociencias y Psicología Experimental; Argentina. Universidad Católica de Cuyo - Sede San Juan. Facultad de Ciencias Médicas; ArgentinaFil: Guevara, Manuel Alejandro. Laboratorio de Neurociencias y Psicología Experimental; Argentina. Universidad Católica de Cuyo - Sede San Juan. Facultad de Ciencias Médicas; ArgentinaFil: Landa, Adriana Inés. Laboratorio de Neurociencias y Psicología Experimental; Argentina. Universidad Católica de Cuyo - Sede San Juan. Facultad de Ciencias Médicas; ArgentinaFil: Lafuente, José Vicente. Universidad del País Vasco; EspañaFil: Mesones, Humberto Luis. Laboratorio de Neurociencias y Psicología Experimental; Argentina. Fundación Instituto de Neurobiología; Argentina. Universidad Católica de Cuyo - Sede San Juan. Facultad de Ciencias Médicas; ArgentinaFil: Gargiulo, Pascual Angel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Laboratorio de Neurociencias y Psicología Experimental; Argentina. Universidad Católica de Cuyo - Sede San Juan. Facultad de Ciencias Médicas; Argentin

Effects of cycloleucine in the nucleus accumbens septi on the elevated plus maze test in rats

Abstract Introduction: In recent years, an important number of studies have emphasized the psychopharmacological actions of cycloleucine (1-aminocyclopentanecarboxylic acid) acting on the NR1 subunit (glycine allosteric site) of NMDA (Nmethyl-D-aspartic acid) receptor. We studied the effects of its injection in an anxiety test. Methods: The elevated plus maze test was used. Male rats bilaterally cannulated into the nucleus accumbens septi (NAS) were employed. Rats were divided into 5 groups that received either 1 µL injections of saline or cycloleucine (0.5, 1, 2, or 4 µg) 15 min before testing. Results: Time spent in the open arm was significantly increased by cycloleucine treatment with all doses (1 and 2 µg, p < 0.05; 0.5 and 4 µg, p < 0.01), like number of extreme arrivals (0.5 and 1 µg, p < 0.05; 2 µg, p < 0.01; and 4 µg, p < 0.001). Open arm entries were increased by the highest dose only (4 µg, p < 0.01). Discussion/Conclusion: Present results show no difference between all doses in the time spent in the open arm, suggesting an indirect, noncompetitive action of the drug. The increase in extreme arrivals and open arm entries suggests a dose influence in these parameters. We conclude that cycloleucine influence on the NMDA receptors within NAS leads to anxiolytic-like effects and behavioral disinhibition, which once more confirms the involvement of NAS in anxiety processing.Fil: Gargiulo, Augusto P.I.. Universidad Nacional de Cuyo; ArgentinaFil: Acuña, Andres. Universidad Nacional de Cuyo; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza; ArgentinaFil: Gargiulo, Mercedes Maria Lucrecia. Universidad Nacional de Cuyo; ArgentinaFil: Gargiulo, Ángel José Martín. Universidad Nacional de Cuyo; ArgentinaFil: Gargiulo, Marcos C. J.. Universidad Nacional de Cuyo; ArgentinaFil: Baiardi, Gustavo Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; ArgentinaFil: Mora, Sergio. Universidad de Chile; ChileFil: Lafuente, José Vicente. Universidad del País Vasco; EspañaFil: Romanowicz, Esteban Alejandro. Universidad Nacional de Cuyo; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza; ArgentinaFil: Landa, Adriana. Universidad Nacional de Cuyo; ArgentinaFil: Guevara, Manuel Alejandro. Universidad Nacional de Cuyo; ArgentinaFil: Gargiulo, Pascual Angel. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Departamento de Patología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza; Argentin