Roger Godbout

Restless legs syndrome and periodic leg movements in sleep : the primary role of dopaminergic mechanism

We report here the possible effect of opiates on a patient exhibiting particularly severe restless legs syndrome (RLS) and periodic leg movements in sleep (PLMS). This patient was investigated in the sleep laboratory under three conditions, namely, unmedicated (baseline), medicated with codeine sulfate, and medicated with both codeine sulfate and pimozide. Codeine sulfate dramatically improved abnormal motor behavior in this patient. The addition of pimozide reversed the beneficial effect of codeine during the Forced Immobilization Test but not in spontaneous RLS or PLMS at night. These results are discussed in view of the possible involvement of the dopaminergic mechanism in RLS/PLMS syndrome.

Restless legs syndrome and periodic movements in sleep: physiopathology and treatment with L-dopa

Seven patients suffering from restless legs syndrome (RLS) and periodic movements in sleep (PMS) were investigated before and after treatment with L-Dopa. The effect of treatment was evaluated by polysomnography, structured interviews, and daily questionnaires. Sleep organization and subjective complaints improved during treatment with 100 to 200 mg of L-Dopa. Polysomnographic recordings also revealed a significant decrease of periodic leg movements during the first third of the night and a rebound during the last third. These results and previous biochemical findings raise the hypothesis that RLS and PMS may both result from reduced dopaminergic activity in the CNS, perhaps resulting from decreased sensibility of postsynaptic receptors.

Sleep architecture and its clinical correlates in first episode and neuroleptic-naive patients with schizophrenia

The goal of the present study was to characterize sleep organization in first episode and neuroleptic-naive patients with schizophrenia and to evaluate relationships between those sleep parameters and clinical symptoms. Eleven patients with acute schizophrenia never treated with neuroleptics were compared to 11 healthy controls. Sleep stages and phasic events (sleep spindles and rapid-eye-movements during REM sleep (REMs) were visually identified. Clinical symptoms were assessed using the Brief Psychiatric Rating Scale (BPRS). Compared to controls, patients with schizophrenia had difficulty initiating sleep, decreased stage 4 duration, reduced rapid eye movement (REM) sleep latency, and normal sleep spindles and REMs densities. Positive symptoms correlated negatively with REM sleep latency. The BPRS total score correlated negatively with REM sleep duration and REMs density. The present results indicate that first episode and neuroleptic-naive patients with schizophrenia have difficulties initiating, but not maintaining, sleep. These results also confirm that the duration of stage 4 and REM sleep latency are reduced in first episode and neuroleptic-naive patients with schizophrenia. The fact that measures of REM sleep correlate with clinical scales of schizophrenia suggests that REM sleep physiology shares common substrates with symptoms of this disease.

The treatment of the restless legs syndrome with clonazepam: a prospective controlled study

The effect of clonazepam on the restless legs syndrome was studied in a group of 6 patients. Following a drug-free period, 3 patients received clonazepam for 4 weeks followed by placebo for 4 weeks thereafter and 3 patients received the same medication and for the same length of time but in reverse order. The effectiveness of the medication was evaluated by means of a self-rating system in which patients assigned a score daily to the degree of discomfort experienced in the previous 24 hours. Three patients improved on clonazepam but 2 of these also improved on placebo. Clonazepam was not shown to be significantly more effective than placebo in the treatment of RLS.

Effects of gestational stress: 1. Evaluation of maternal and juvenile offspring behavior

In both humans and animals, stress experienced during gestation is associated with physiological changes and disruptions in emotional function and cognitive ability in offspring; however, much less is known about the effects of such stress in mothers. In animal models, physical restraint is commonly employed to induce stress during gestation and results in elevated postpartum maternal anxiety and changes in maternal care. The purpose of the current study was to evaluate the consequences of restraint stress applied on gestation days 10 through 19 in mother rats and their juvenile offspring. Progeny were reared by birth mothers. Preterm anxiety was assessed in the elevated plus maze and maternal behavior in the retrieval test. Cognitive (T-maze) and anxiety measures (elevated plus maze and emergence) were applied to a subset of male and female offspring at 30-31 days of age. Weight and litter characteristics were also recorded. Mother rats exposed to stress during gestation had attenuated weight gain, elevated anxiety-like behavior, and reduced maternal care. Stressed mothers also had fewer pups and an elevated offspring mortality rate. The consequences of gestational stress in offspring were subtle and gender-dependent. Only juvenile females displayed marginal effects of gestational stress in the form of elevated anxiety-like behavior and attenuated weight gain. In the current study, although gestational stress had robust effects in the mother rat, these did not translate to similar changes in offspring behavior. The importance of focusing research on maternal responses to gestational stress is highlighted by these findings.

Behavioural signs of depression and apoptosis in the limbic system following myocardial infarction: effects of sertraline

Abstract Depression is diagnosed in 15–30% of patients following myocardial infarction (MI) and this may also be observed in the rat. We measured the effects of the antidepressant sertraline on behavioural and biochemical events following MI in a rat model. Following surgery, MI rats and sham controls were treated with sertraline (10 mg/kg, i.p.) or saline. Subgroups of rats were tested for behavioural depression 14 days after surgery. Apoptosis was estimated in other rats by measuring caspase-3 activity and TUNEL positive cells (3 days after surgery) in limbic structures (amygdale, hippocampus, hypothalamus, frontal and prefrontal cortices). Bax/Bcl-2 ratio was measured 14 days after surgery. Behavioural signs of depression (decreased sucrose intake and forced swimming time) were found in saline-treated MI rats but not in sertraline-treated rats. Compared with controls, caspase-3 activity and TUNEL positive cells were significantly increased in most limbic structures of MI rats. High prefrontal Bax/Bcl-2 ratio in MI rats correlated with low forced swimming time. Apoptosis was not found in sertraline-treated MI rats. These results establish the bases of a rat model of depression following MI and show for the first time that a selective serotonin reuptake inhibitor prevents both behavioural and biochemical markers in this model.

Combination of Lactobacillus helveticus R0052 and Bifidobacterium longum R0175 reduces post-myocardial infarction depression symptoms and restores intestinal permeability in a rat model.

Myocardial infarction (MI) in rats is accompanied by apoptosis in the limbic system and a behavioural syndrome similar to models of depression. We have already shown that probiotics can reduce post-MI apoptosis and designed the present study to determine if probiotics can also prevent post-MI depressive behaviour. We also tested the hypothesis that probiotics achieve their central effects through changes in the intestinal barrier. MI was induced in anaesthetised rats via 40-min transient occlusion of the left anterior coronary artery. Sham rats underwent the same surgical procedure without actual coronary occlusion. For 7 d before MI and between the seventh post-MI day and euthanasia, half the MI and sham rats were given one billion live bacterial cells of Lactobacillus helveticus R0052 and Bifidobacterium longum R0175 per d dissolved in water, while the remaining animals received only the vehicle (maltodextrin). Depressive behaviour was evaluated 2 weeks post-MI in social interaction, forced swimming and passive avoidance step-down tests. Intestinal permeability was evaluated by oral administration with fluorescein isothiocyanate-dextran, 4 h before euthanasia. MI rats displayed less social interaction and impaired performance in the forced swimming and passive avoidance step-down tests compared to the sham controls (P < 0·05). Probiotics reversed the behavioural effects of MI (P < 0·05), but did not alter the behaviour of sham rats. Intestinal permeability was increased in MI rats and reversed by probiotics. In conclusion, L. helveticus R0052 and B. longum R0175 combination interferes with the development of post-MI depressive behaviour and restores intestinal barrier integrity in MI rats.

A laboratory study of sleep in Asperger's syndrome.

Aspergers syndrome (AS) is a pervasive developmental disorder that may fall along the autistic spectrum. We compared the sleep of eight patients with AS with that of participants matched for age and gender. Patients with AS showed decreased sleep time in the first two-thirds of the night, increased number of shifts into REM sleep from a waking epoch, and all but one patient showed signs of REM sleep disruption. EEG sleep spindles were significantly decreased while K complexes and REM sleep rapid eye movements were normal. Three patients with AS, but none of the comparison participants, showed a pathological index of periodic leg movements in sleep. These observations show that sleep disorders are associated with AS and suggest that defective sleep control systems may be associated with the clinical picture of AS.

Effect of gamma-hydroxybutyrate and its antagonist NCS-382 on spontaneous cell firing in the prefrontal cortex of the rat

Gamma-hydroxybutyrate (GHB) at low doses (5-10 mg/kg i.p.) increased and at high doses (160-320 mg/kg i.p.) decreased the spontaneous firing rate of prefrontal cortex (PFC) neurons recorded in urethane-anesthetized rats. Only excitations were blocked by NCS-382, a specific GHB receptor antagonist; this suggests that the excitatory effect of low doses of GHB is mediated by a GHB receptor whereas the inhibitory effect of high doses of GHB involves a more complex mechanism.

Nocturnal γ-hydroxybutyrate. Effect on periodic leg movements and sleep organization of narcoleptic patients

Periodic leg movements during sleep (PMS) is a disorder frequently encountered in narcolepsy. In the present study, 12 narcoleptic patients (six with PMS and six without) were recorded in a sleep laboratory for 2 consecutive nights before and after treatment with gamma-hydroxybutyrate (GHB) taken at bedtime for 1 month. Treatment resulted in decreased rapid eye movement (REM) sleep latency and increased REM efficiency without change in the total duration of REM sleep. GHB was associated with the appearance of pathological levels of PMS in patients who were unaffected before treatment. These results are discussed in relation to the role of dopamine in the physiopathology of narcolepsy and PMS.