Mucopolysaccharidosis type I (MPS I) is one of the most common lysosomal storage diseases with progressive neurological dysfunction. To characterize the chronological behavioral profiles and identify the onset of functional deficits in a MPS I mouse model (IDUA −/− ), we evaluated anxiety, locomotor behavior, startle, spatial learning and memory with mice at 2-, 4-, 6-and 8-months of age. In automated open-field test, IDUA −/− mice showed hypoactivity as early as 2-months of age and altered anxiety starting from 6-months of age during the initial exploratory phase, even through normal habituation was observed at all ages. In the marble-burying task, the anxiety-like compulsive behavior was normal in IDUA −/− mice at almost all tested ages, but significantly reduced in 8-month old male IDUA −/− mice which coincided with the rapid death of IDUA −/− males starting from 7-months of age. In the Morris water maze, IDUA −/− mice exhibited impaired proficient learning only at 4-months of age during the acquisition phase. Spatial memory deficits were observed in IDUA −/− mice during both 1-and 7-days probe trials at 4-and 8-months of age. The IDUA −/− mice performed normally in a novel object recognition task at younger ages until 8 month old when reduced visual cognitive memory retention was noted in the IDUA −/− mice. In addition, 8-month old IDUA −/− mice failed to habituate to repeated open-field exposure, suggesting deficits in nonaversive and non-associative memory. In acoustic startle assessment, significantly more non-responders were found in IDUA −/− , but normal performance was seen in those that did show a response. These results presented a temporal evaluation of phenotypic behavioral dysfunctions in IDUA −/− mice from adolescent to maturity, indicating the impairments, with different age of onset, in locomotor and anxiety-like compulsive behaviors, spatial learning and memory, visual recognition, and short-term non-associative memory retention. This study would also provide guidelines for the experimental designs of behavioral evaluation on innovative therapies for the treatment of MPS type I.

Ten chronic undifferentiated schizophrenics, 6 men and 4 women, aged 28–63, with 6- to 31-year histories of the disease were given DDAVP to observe the effects of this neuropeptide on the prevalent negative symptoms of their illness. Patients were maintained on neuroleptic therapy and first given a 20-day course of placebo followed by 20 days of DDAVP i.m., 4 µg. Andreasen Scale for assessment of negative symptoms, the Brief Psychiatric Rating Scale, the NOSIE Rating Scale and the Luria-Nebraska Rating Scale were administered to monitor negative symptomatology, behavior and memory before the study began, after placebo and after DDAVP administration. Patients were also given a growth hormone-clonidine test and in addition plasma basal concentrations of 3-methoxy-4-hydroxyphenylglycol (MHPG), homovanillic acid, 3,4-dihydroxyphenylacetic acid (DOPAC) and 5-hydroxyindoleacetic acid (5-HIAA) were measured at the same intervals. DDAVP therapy induced a significant improvement of negative symptomatology and a trend toward improvement of short- to medium-term memory. No changes in homovanillic acid, MHPG, 5-HIAA and DOPAC, nor of growth hormone response to clonidine stimulation were observed.

SummaryNimodipine was administered at the daily dose of 90 mg po, for 30 days, to ten chronic undifferentiated schizophrenics, eight men and two women, aged 31-35 years, maintained on previously longlasting neuroleptic treatments. In five patients, a placebo period of 15 days preceded the administration of the drug. Monitoring of psychiatric symptomatology by the Brief Psychiatric Rating Scale (BPRS) revealed significant nimodipine-induced improvement. However, the Andreasen Rating Scale for Positive Symptoms (SAPS) showed favourable effects only in the five patients who had not received placebo, while in the others both SAPS and the Andreasen Rating Scale for Negative Symptoms (SANS) showed no significant effect of therapy. The Tardive Dyskinesia Scale revealed no improvements of neurological symptoms after either placebo or drug treatment. Measurement of plasma MHPG concentrations revealed no significant changes induced by either placebo or nimodipine, while HVA plasma levels showed a trend toward decrease, and prolactin a trend toward increase, after nimodipine.