piperidines and Developmental-Disabilities

Rapid eye movement (REM) sleep is greatest in the developing brain, is driven by acetylcholine, and may represent a protected time for neuroplasticity. Recently published data from our lab observed that children with autism spent significantly less time in this state during a single night recording than did typically developing children and those with developmental delay without autism. The objective of this study was to determine whether or not donepezil can increase the REM % in children with diagnosed autism spectrum disorder (ASD) found to have REM % values of at least two standard deviations below expected for age.. Five subjects found to have an ASD (ages 2.5-6.9 years) and demonstrated deficits in REM sleep compared with within-lab controls were enrolled in a dose finding study of donepezil. Each subject was examined by polysomnography for REM sleep augmentation after drug administration.. REM sleep as a percentage of Total Sleep Time was increased significantly and REM latency was decreased significantly after drug administration in all subjects. No other observed sleep parameter was changed significantly.. Donepezil can increase the amount of time that children with an ASD spend in the REM sleep state. A double-blind, placebo-controlled trial is needed to assess the association between REM sleep augmentation and learning, cognition, and behavior in such children.

Topics: Autistic Disorder; Child; Child Development Disorders, Pervasive; Child, Preschool; Developmental Disabilities; Donepezil; Dose-Response Relationship, Drug; Electrocardiography; Humans; Indans; Male; Nootropic Agents; Piperidines; Polysomnography; Sleep; Sleep Wake Disorders; Sleep, REM; Treatment Outcome

Current concepts suggest that exposure to THC during adolescence may act as a risk factor for the development of psychiatric disorders later in life. However, the molecular underpinnings of this vulnerability are still poorly understood. To analyze this, we investigated whether and how THC exposure in female rats interferes with different maturational events occurring in the prefrontal cortex during adolescence through biochemical, pharmacological and electrophysiological means. We found that the endocannabinoid system undergoes maturational processes during adolescence and that THC exposure disrupts them, leading to impairment of both endocannabinoid signaling and endocannabinoid-mediated LTD in the adult prefrontal cortex. THC also altered the maturational fluctuations of NMDA subunits, leading to larger amounts of gluN2B at adulthood. Adult animals exposed to THC during adolescence also showed increased AMPA gluA1 with no changes in gluA2 subunits. Finally, adolescent THC exposure altered cognition at adulthood. All these effects seem to be triggered by the disruption of the physiological role played by the endocannabinoid system during adolescence. Indeed, blockade of CB1 receptors from early to late adolescence seems to prevent the occurrence of pruning at glutamatergic synapses. These results suggest that vulnerability of adolescent female rats to long-lasting THC adverse effects might partly reside in disruption of the pivotal role played by the endocannabinoid system in the prefrontal cortex maturation.

Topics: Age Factors; Animals; Cannabinoid Receptor Agonists; Cyclohexanols; Developmental Disabilities; Dizocilpine Maleate; Dronabinol; Estradiol; Estrous Cycle; Excitatory Amino Acid Antagonists; Female; In Vitro Techniques; Neurites; Piperidines; Prefrontal Cortex; Pyrazoles; Radionuclide Imaging; Rats; Rats, Sprague-Dawley; Receptors, Glutamate; Synaptic Potentials; Tritium

Topics: Abnormalities, Multiple; Adjuvants, Anesthesia; Anesthetics, Inhalation; Anesthetics, Intravenous; Atropine; Cleft Palate; Developmental Disabilities; Face; Female; Humans; Infant; Intellectual Disability; Intubation, Intratracheal; Methyl Ethers; Microcephaly; Midazolam; Muscle Hypotonia; Nitrous Oxide; Piperidines; Remifentanil; Sevoflurane; Syndrome