Effects of Cycloleucine in the Nucleus Accumbens Septi on the Elevated plus Maze Test in Rats

Abstract

<b><i>Introduction:</i></b> 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 (N-methyl-D-aspartic acid) receptor. We studied the effects of its injection in an anxiety test. <b><i>Methods:</i></b> 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. <b><i>Results:</i></b> Time spent in the open arm was significantly increased by cycloleucine treatment with all doses (1 and 2 µg, <i>p</i> < 0.05; 0.5 and 4 µg, <i>p</i> < 0.01), like number of extreme arrivals (0.5 and 1 µg, <i>p</i> < 0.05; 2 µg, <i>p</i> < 0.01; and 4 µg, <i>p</i> < 0.001). Open arm entries were increased by the highest dose only (4 µg, <i>p</i> < 0.01). <b><i>Discussion/Conclusion:</i></b> 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.

Anxiolytic-like effects of Atenolol injected into the nucleus accumbens septi in rats after restrain stress in the elevated plus maze test

“…The NAS shows here, once again, its role in modulating anxiety. These findings increase and enriches our previous findings of NAS function (Gargiulo, 1996(Gargiulo, , 2003Landa de Gargiulo, 2004, 2014;Baiardi et al, 2007). An additional goal of the present study is related to the role of NAS and the specific behavioural profile in anxiety under stress conditions.…”

“…They were tested under stress conditions. In this schedule, an anxiolytic-like effect was induced injecting the atenolol acutely in the NAS, giving additional evidence of its role in anxiety modulation, as we have previously postulated (Gargiulo et al, 2018;Kelley et al, 2003;Martínez at el, 2002aMartínez at el, , 2002bGargiulo and Landa de Gargiulo, 2004;Llano López et al, 2012, 2013Gargiulo et al, 2020).…”

“…The role of Corticotropin Releasing Hormone (CRH) is relevant in anxiety mediation. We have shown that intracerebroventricular injection of this peptide induces an increase in anxiety levels in the EPM, and significant increases in some specific patterns of grooming behavior (Gargiulo and Donoso, 1989;1996).…”

“…These facts are closely related to a decrease in corticotropin-releasing factor gene expression in the amygdala (Van Bockstaele et al, 2006;Schank et al, 2008;Rudoy et al, 2009;Gargiulo et al, 2020). These groups have proposed that the amygdala is a relevant neural substrate in the processes of interaction between β-1 adrenergic receptor and corticotropin-releasing factor and its corresponding gene expression (Van Bockstaele et al, 2006;Rudoy et al, 2009).…”

“…Parameters and methods of our previous studies were maintained (Martínez et al, 2002a;Gargiulo et al, 2018;Gargiulo and Donoso, 1989;1996;Laconi et al, 2001;Llano López et al, 2012;2013;Gargiulo et al, 2020). We measured classical parameters of our lab, according to our previous studies.…”