Reagents and conditions: (a) SeO₂, t-BuOOH, CH₂Cl₂, r.t; (b) DAST, CH₂Cl₂, 0°C.

<p>Reagents and conditions: (a) SeO₂, t-BuOOH, CH₂Cl₂, r.t; (b) DAST, CH₂Cl₂, 0°C.</p

Effect of 1 (1, 3 and 10 mg/kg, n = 7, 6 and 15 animals, respectively) in Swiss male mice tested in the pre-pulse inhibition model.

<p>Animals received a first injection of vehicle (V) or <b>1</b> followed, 30 min later, by vehicle (n = 9) or amphetamine 10mg/kg (V+amphetamine group = 11 animals). *indicates difference from V+V group. + indicates difference from V+amphetamine group (ANOVA followed by the Duncan test, p<0.05).</p

Lack of effect of 3 (10 and 30 mg/kg, n = 7–8 animals/group) in Swiss male mice tested in the pre-pulse inhibition model.

<p>Animals received a first injection of vehicle (V) or <b>3</b> followed, 30 min later, by vehicle (n = 7) or amphetamine 10 mg/kg (V+amphetamine group = 7 animals). Data represents the means+SEM. *indicates difference from V+V group (ANOVA followed by the Duncan test, p<0.05).</p

Lack of effect of 2 (10, 30 and 60 mg/kg, n = 7–8 animals/group) in Swiss male mice tested in the pre-pulse inhibition model.

<p>Animals received a first injection of vehicle (V) or 2 followed, 30 min later, by vehicle (n = 12) or amphetamine 10 mg/kg (V+amphetamine group = 11 animals). *indicates difference from V+V group (ANOVA followed by the Duncan test, p<0.05).</p

CBD (30–60 mg/kg, n = 10–11 animals/group), HUF-101 (10 mg/kg, n = 13–14 animals/group) and fluoxetine (10 mg/kg, n = 10 animals) decreased the number of buried marbles in the MBT test.

<p>*indicates difference from V+V group (ANOVA followed by the Duncan test, p<0.05).</p

Reagents and conditions: (a) 1-fluoropyridinium triflate, CH₂Cl₂, r.t.

<p>Reagents and conditions: (a) 1-fluoropyridinium triflate, CH₂Cl₂, r.t.</p

Effect of 3 (1, 3 and 10 mg/kg, n = 5, 5 and 6 animals, respectively) in Swiss male mice tested in the forced swim test (FST, upper panel) and elevated plus maze (EPM).

<p>*indicates difference from V group (ANOVA followed by the Duncan test, p<0.05). Further specification as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0158779#pone.0158779.g004" target="_blank">Fig 4</a>.</p

Lack of effect of 5a (3, 10 and 30 mg/kg, n = 8 animals/group) in Swiss male mice tested in the pre-pulse inhibition model.

<p>Animals received a first injection of vehicle (V) or <b>5a</b> followed, 30 min later, by vehicle or amphetamine 10 mg/kg (V+amphetamine). *indicates difference from V+V group (ANOVA followed by the Duncan test, p<0.05). Further specifications as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0158779#pone.0158779.g007" target="_blank">Fig 7</a>.</p

Effects of sodium nitroprusside in the prevention of schizophrenia-like symptoms induced by ketamine – A translational double-blind study

<div><p>Abstract Background: Recent evidence has shown improvements in schizophrenia symptoms after the infusion of sodium nitroprusside (SNP), a nitric oxide (NO) donor. In the rat model of schizophrenia using ketamine injection, pretreatment with SNP seems to prevent behavioral changes associated with positive symptoms for up to one week. Objective: We investigated whether SNP would have preventative effects on psychogenic symptoms induced by ketamine in healthy subjects. Methods: Healthy subjects (N = 38) were assigned to distinct groups that received SNP in different doses (0.15, 0.25, and 0.5 mcg/kg/min). First, participants received an infusion of SNP or placebo over 75 minutes. After 10 minutes, they were injected for 1 minute with a bolus of 0.26 mg/kg of ketamine and a maintenance dose was started 5 minutes later, with 0.25 mg/kg/h of ketamine for 50 minutes. Results: Ketamine-induced psychopathological alterations induced were reduced by SNP, as assessed with the Brief Psychological Rating Scale. Scores in the objective subscale of the Clinician-Administered Dissociative States Scale were also lower in SNP sessions compared to placebo. SNP had protective effects against deterioration in facial emotion and identity recognition tasks induced by ketamine. Discussion: Our findings support the view that SNP has preventative properties against psychotic manifestations.</p></div