Adolescent Ethanol Exposure Alters Cholinergic Function and Apical Dendritic Branching Within the Orbital Frontal Cortex.

During adolescence, heavy binge-like ethanol consumption can lead to frontocortical structural and functional impairments. These impairments are likely driven by adolescence being a critical time point for maturation of brain regions associated with higher-order cognitive functioning. Rodent models of heavy binge-like ethanol exposure show consistent disruptions to the typical development of the prefrontal cortex (PFC). All deep cortical layers receive cholinergic projections that originate from the Nucleus basalis of Meynert (NbM) complex. These cholinergic projections are highly involved in learning, memory, and attention. Adolescent intermittent ethanol exposure (AIE) induces cholinergic dysfunction as a result of an epigenetic suppression of the genes that drive the cholinergic phenotype. The current study used a model of AIE to assess structural and functional changes to the frontal cortex and NbM following binge-like ethanol exposure in adolescence. Western blot analysis revealed long-term disruptions of the cholinergic circuit following AIE: choline acetyltransferase (ChAT) was suppressed in the NbM and vesicular acetylcholine transporter (VAChT) was suppressed in the orbitofrontal cortex (OFC). In vivo microdialysis for acetylcholine efflux during a spatial memory task determined changes in cholinergic modulation within the PFC following AIE. However, AIE spared performance on the spatial memory task and on an operant reversal task. In a second study, Golgi-Cox staining determined that AIE increased apical dendritic complexity in the OFC, with sex influencing whether the increase in branching occurred near or away from the soma. Spine density or maturity was not affected, likely compensating for a disruption in neurotransmitter function following AIE.

Preliminary evaluation of epidural morphine for treatment of heroin withdrawal.

OBJECTIVE: To evaluate the efficacy of epidural morphine in treating heroin withdrawal in patients who failed to detoxify by the other methods. DESIGN: Prospective study. SETTING: Department of Psychiatry of a general hospital. PATIENTS: 8 ASA physical status I patients, aged 26 to 42 years, not having concurrent diseases requiring medication, and who had previously failed other methods of detoxification. INTERVENTIONS: Epidural catheters were inserted at the L(3)-L(4) interspace. Bolus injections of morphine sulfate, 3.0 mg in normal saline, were administered epidurally at 24-hour intervals. Treatment continued for 10 to 12 days. MEASUREMENTS: Withdrawal symptoms, such as mydriasis, insomnia, rhinorrhea, arthralgia, muscular pain, tooth pain, vomiting, diarrhea, dysphoria, and drug craving were monitored. MAIN RESULTS: Withdrawal symptoms ceased within 10 days. Withdrawal symptoms were diminished or entirely abolished by the treatment, and no patient requested to drop out of the program. Discontinuation of the epidural injections did not cause relapse of withdrawal. All patients reported that withdrawal with epidural morphine was considerably easier compared to other methods that they had previously experienced. CONCLUSIONS: A preliminary evaluation of epidural morphine in addicts that failed previous detoxifications showed high effectiveness of this method in reducing withdrawal symptoms.

A gene for autosomal recessive spondylocostal dysostosis maps to 19q13.1-q13.3.

In spondylocostal dysostosis (SD), vertebral-segmentation defects are associated with rib anomalies. This results in short-trunk short stature, nonprogressive kyphoscoliosis, and radiological features of multiple hemivertebrae and rib fusions. SD can be familial, and both autosomal dominant and autosomal recessive (AR) inheritance have been reported, but no genes have been identified or localized for nonsyndromic SD in humans. We performed genomewide scanning by homozygosity mapping in a large consanguineous ARSD Arab Israeli family with six definitely affected members. Significant linkage was found to chromosome 19q13, with a LOD score of 6.9. This was confirmed in a second Pakistani family with three affected members, with a LOD score of 2.4. The combined-haplotype data identify a critical region between D19S570 and D19S908, an interval of 8.5 cM on 19q13.1-19q13.3. This is the first study to localize a gene for nonsyndromic SD. ARSD is clinically heterogeneous and is likely to result from mutations in developmental genes or from regulating transcription factors. Identification of these genes will improve the understanding of the molecular processes contributing to both normal and abnormal human vertebral development.