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

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 (N-methyl-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.

Effects of antidepressants and soybean association in depressive menopausal women.

Depression in menopausal women has been widely described for many years ago and is related to hormonal decrease, mainly estrogens. The use of soy has been proposed as a possible coadjutant alternative to treat menopausal depressive disorder. In the present pilot clinical trial the effect of soybean, antidepressants and the association of soybean with antidepressants was studied in 40 depressive menopausal women for three months. Patients were divided in four groups of 10 women: fluoxetine (10 mg), soybean (100 mg), sertraline (50 mg), and sertraline (50 mg) plus soybean (100 mg). The Hamilton and Zung Depression Scales were used to measure the treatment effects. Values at the beginning and at the end of the study were compared. In all cases a significant difference was observed when the treated groups were compared vs. their untreated situation in both scales (p < 0.001). When a comparison between pre- minus post-treatment Zung scale scores was done, the effect induced by the association of sertraline and soybean was significantly higher than the other groups (p < 0.05). These effects were also seen using the Hamilton scale scores, showing significant differences between the association vs. soybean (p < 0.05) and setraline (p < 0.05) groups, but not vs. fluoxetine group. We conclude that soybean has an antidepressant effect per se, and the association of soybean and antidepressants increases their effects.

Effects of atenolol injected into the nucleus accumbens septi in rats in the elevated plus-maze test.

Background In previous studies, we have observed that glutamate antagonists injected within the nucleus accumbens septi (NAS) induced an anxiolytic-like effect in the elevated plus maze (EPM) test in rats. In the present study, the effect of Atenolol, a specific Beta Adreno-receptor antagonist in the EPM was studied in male rats bilaterally cannulated NAS. Methods Rats were divided into five groups that received either 1 µL injections of saline or atenolol in different doses (0.75, 1 or 2 µg/1 µL, n=15-16) 15 min before testing. Results Time Spent in the Open Arm was modified by treatment (F=4.563, p=0.006, df 3). This was increased by the lowest dose of atenolol (p<0.05), by the medium doses (p<0.001) and also by the highest dose (p<0.01). Time per Entry was modified by treatment (F=4.54, p=0.06, df 3). This parameter was increased by the lowest dose of atenolol (p<0.01), but not for the medium and higher doses. Conclusions We conclude that Atenolol beta receptor blockade in the accumbens lead to an anxiolytic-like effect related to an increase in the time spent in the open arm and in the time per entry, showing specific behavioral patterns.

AP-7 into the nucleus accumbens disrupts acquisition but does not affect consolidation in a passive avoidance task.

The effect of the blockade of N-methyl-D-aspartic acid (NMDA)-type glutamatergic receptors in the nucleus accumbens septi (Acc) during different phases of a passive avoidance task (step-through paradigm, two chambers) of learning was studied in male rats which had been bilaterally cannulated into the Acc. Animals were trained with a punishment procedure (3 s shock of 1 mA) to avoid one of the chambers. The rats received either saline or (+/-)2-amino-7-phosphonoheptanoic acid (AP-7) solution (1 microg/1 microl) 10 min before training (pretraining schedule) or immediately after the shock (posttraining schedule). In the test phase, the animals were placed back into the white chamber after 1 and 8 days later. In this moment, rats stayed there for 1 min, after which the time elapsed between the removal of the door to the introduction into the dark chamber of the head (Latency 1) and body (Latency 2) and fecal boli expelled were recorded. In the pretraining injection schedule, the drug treatment significantly reduced Latency 2 (P<.05) and fecal boli (P<0.01) on Day 1, and all parameters on Day 8 (P<.05). The posttraining injection schedule did not modify behavior. We conclude that a preshock NMDA-glutamatergic blockade of the Acc leads to cognitive disturbances during acquisition and a decrease in anxiety levels, but that the consolidation of a learned task is not affected by postshock administration.

Effects of selective NMDA and non-NMDA blockade in the nucleus accumbens on the plus-maze test.

Effect of blocking N-methyl-D-aspartic acid (NMDA) and non-NMDA-glutamatergic receptors on performance in the plus-maze was studied in male rats bilaterally cannulated into the nucleus accumbens (Acc). Rats were divided into seven groups that received either 1 microl injections of saline, (+/-)2-amino-7-phosphonoheptanoic acid (AP-7, 0.2, 0.5, or 1 microg) or 2,3 dioxo-6-nitro-1,2,3,4,tetrahydrobenzo-(f)quinoxaline-7-sulphonamide disodium (NBQX, 0.2, 0.5, or 1 microg) 15 min before testing. Time spent in open arm, time per entry, end arrivals, open, closed, and total arm entries, relationship between open-, closed-, and total arm entries, rearing, face-, head-, and body grooming, and number of fecal boli were recorded. Time spent in the open arm increased under AP-7 (0.5 and 1 microg; P<.01) and NBQX (1 microg; P<.05) treatment, whereas time per entry was increased only with AP-7 (1 microg; P<.05). Open arm entries were increased by the intermediate doses of AP-7 (0.5 microg; P<.01) and NBQX (0.5 microg; P<.05); end arrivals were increased by the intermediate dose of AP-7 (0.5 microg/1 microl, P<.05). The frequency of rearing, grooming, and closed arm entries was not affected by the treatment. We conclude that NMDA and non-NMDA-glutamatergic blockade in the Acc lead to a behavioral disinhibition of cortical influences with the median doses, but that at higher doses the blockers have an anxiolytic-like effect.

Anxiolytic-like effect of losartan injected into amygdala of the acutely stressed rats.

It has been recognized that the stress-related peptides are involved in anxiety states. Angiotensin II receptor blockade by systemic administration of the AT(1) receptor antagonists has been proposed as a new treatment possibility for anxiety disorders. For better understanding of the related mechanisms, in this study we evaluated effects of bilateral intraamygdaloid injections of 2 (LOS 2) and 4 (LOS 4) µg of losartan (LOS), a selective AT(1) receptor antagonist, on the behavior of the not stressed and acutely stressed rats in an elevated "plus" maze. Under non-stress conditions, LOS 4 increased time spent in the open arms (p < 0.01), number of extreme open arm arrivals (p < 0.05), time per entry (p < 0.01), and the number of total arm entries (p < 0.05) showing thus considerable anxiolytic activity. The open arm extreme arrivals were increased by LOS 4 in both not stressed (p < 0.05) and stressed (p < 0.05) rats. When no stressed and stressed LOS 4 animals were compared, time per entry and the number of closed arm entries (p < 0.05, both) were decreased in the latter group. Moreover, the LOS 4 stressed rats had significantly increased open/closed arm quotient (p < 0.05) as compared to the both control and LOS 4 non-stress group (p < 0.05, both). These findings suggest that the AT(1) receptor blockade in amygdala is important for the anxiolytic action of LOS (and probably other AT(1) receptor blockers) under both non-stress and stress conditions.