Emotional, cognitive and neurochemical alterations in a premotor stage model of Parkinson's disease.

In addition to classic motor symptoms, Parkinson's disease (PD) is characterized by cognitive and emotional deficits, which have been demonstrated to precede motor impairments. The present study addresses the question of whether a partial degeneration of dopaminergic neurons using 6-hydroxydopamine (6-OHDA) in rats is able to induce premotor behavioral signs. The time-course of nigrostriatal damage was evaluated by tyrosine hydroxylase immunohistochemistry and the levels of dopamine, noradrenaline, and 5-HT in various brain regions were analyzed by high performance liquid chromatography (HPLC). Behavioral tests that assessed a variety of psychological functions, including locomotor activity, emotional reactivity and depression, anxiety and memory were conducted on 6-OHDA lesioned rats. Bilateral infusion of 6-OHDA in the striatum of rats caused early (1 week) damage of dopaminergic terminals in striatum and in cell bodies in substantia nigra pars compacta. The nigrostriatal lesion was accompanied by early loss of dopamine in the striatum, which remained stable through a 3-week period of observation. In addition, a late (3 weeks) loss of dopamine in the prefrontal cortex, but not in the hippocampus, was seen. Additional noradrenergic and serotonergic alterations were observed after 6-OHDA administration. The results indicated that 6-OHDA lesioned rats show decreased sucrose consumption and an increased immobility time in the forced swimming test, an anhedonic-depressive-like effect. In addition, an anxiogenic-like activity in the elevated plus maze test and cognitive impairments were observed on the cued version of the Morris water maze and social recognition tests. These findings suggest that partial striatal dopaminergic degeneration and parallel dopaminergic, noradrenergic and serotonergic alterations in striatum and prefrontal cortex may have caused the emotional and cognitive deficits observed in this rat model of early phase PD.

[Risk management in the USA]. / Risk Management in den USA.

In the US and even within healthcare, Risk Management as a concept has existed for a long time--however, never as formally as it exists today. The change in how risk is identified and managed in hospitals and within medical care has evolved considerably in just the last 25 years. Risk management took on increased importance with the medical malpractice crisis the US experienced in the mid-1970s. Up until then, it appears its primary function had been to economically transfer risk. With the advent of managed care, risks have been recognized as generators of considerable potential cost to the healthcare system and one that must be proactively managed. Today, the successful management of risk is an essential part of healthcare administration.

Effects of SR141716A on Cognitive and Depression-Related Behavior in an Animal Model of Premotor Parkinson's Disease.

A previous study from our laboratory revealed that moderate nigral dopaminergic degeneration caused emotional and cognitive deficits in rats, paralleling early signs of Parkinson's disease. Recent evidence suggests that the blockade of cannabinoid CB(1) receptors might be beneficial to alleviate motor inhibition typical of Parkinson's disease. Here, we investigated whether antagonism of CB(1) receptors would improve emotional and cognitive deficits in a rat model of premotor Parkinson's disease. Depression-like behavior and cognition were assessed with the forced swim test and the social recognition test, respectively. Confirming our previous study, rats injected with 6-hydroxydopamine in striatum presented emotional and cognitive alterations which were improved by acute injection of SR141716A. HPLC analysis of monoamine levels demonstrated alterations in the striatum and prefrontal cortex after SR141716A injection. These findings suggest a role for CB(1) receptors in the early symptoms caused by degeneration of dopaminergic neurons in the striatum, as observed in Parkinson's disease.