The influence of subchronic administration of the neurosteroid allopregnanolone on sleep in the rat.

The endogenous neurosteroid allopregnanolone has recently been demonstrated to have somnogenic properties that are very similar to those of other agonistic modulators of GABA(A) receptors, especially of short-acting benzodiazepines. Short-acting benzodiazepines are established to rapidly lose their hypnotic effect upon repeated administration. To investigate the tolerance potential of allopregnanolone, we assessed sleep-wake behavior in rats during subchronic treatment (once daily for five days) with placebo or 15 mg/kg allopregnanolone (n = 8 each). The sleep patterns of the placebo and allopregnanolone group did not differ significantly before and after treatment. Throughout the entire treatment period the allopregnanolone group exhibited shorter non-rapid eye movement sleep (non-REMS) latencies, prolonged REMS latencies, longer non-REMS episodes, more pre-REMS and less low-frequency, but higher spindle activity in the electroencephalogram (EEG) within non-REMS than the placebo group. The lack of tolerance effects suggests that allopregnanolone may be an efficacious modulator of sleep-wake behavior over longer time periods than most drugs targeting the benzodiazepine binding site of the GABA(A) receptor.

[Clinical diagnosis in sleep laboratory patients based on ICD-10, DSM-III-R and ICSD classification criteria]. / Klinische Diagnosen bei Schlaflabor-Patienten basierend auf ICD-10-, DSM-III-R- und ICSD- Klassifikationskriterien.

For the diagnosis of sleep disorders, 3 different standardized classification systems are available: the International Statistical Classification of Diseases and Related Health Problems (ICD-10), the Diagnostic and Statistical Manual of Mental Disorders (DSM-III-R/DSM-IV) and the International Classification of Sleep Disorders (ICSD). These 3 classification schemata were comparatively evaluated in 50 sleep-disturbed patients who were admitted within 1 year to a non-specialized sleep laboratory for diagnostic evaluation and treatment. 17 female and 33 male sleep-disturbed patients, aged 54 +/- 12 years, were recorded polysomnographically in 3 subsequent nights (adaptation night, baseline/diagnosis night, treatment night) for measuring objective sleep quality. The subjective sleep quality as well as the subjective and objective awakening quality was assessed by means of rating scales, as well as psychometric and psychophysiological test battery. During the day, EEG, EEG-mapping, psychodiagnostic tests as well as, in many cases, pulmonary function, otolaryngological, CT, MRT and pharyngometric investigations were carried out. Psychic disorders were the leading cause for sleep problems in all 3 classification systems. Based on the ICD-10, the most frequent diagnosis was non-organic insomnia (46%), followed by sleep apnea (18%) and other organic sleep disorders (14%). Based on the DSM-III-R, 46% of the patients were diagnosed as insomnias based on another mental disorder, 38% as organic hypersomnias and 14% as parasomnias. Based on the ICSD Classification, sleep disorders associated with anxiety disorders were leading (30%), followed by sleep disorders based on affective disorders (16%), obstructive snoring (14%), primary snoring (8%) and sleep disorders based on neurological disorders (6%). While the broader ICD-10 and DSM-III-R diagnoses are syndrome-etiologically oriented and may be easily utilized by the practicing physician, the more narrowly defined, extensive, pathogenetically oriented polysomnographic features including ICSD diagnoses are suited better for the specialist.