Behavioural brain research
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The causes of nigrostriatal neuron degeneration in Parkinson's disease (PD) are not known, but it has been suggested that exogenous or endogenous factors or neurotoxins may play a role. The degree of vulnerability to neurotoxins or other potential mediators of nigral dopamine cell death is thought to be important in understanding Parkinson's disease. In most animal models, the rate of terminal degeneration and corresponding functional impairment is too rapid to investigate effectively either cell vulnerability or the potential benefits of some neuroprotective treatments. ⋯ An immunocytochemical assay for tyrosine hydroxylase, a dopamine cell marker, revealed a partial loss of immunoreactive cells in the substantia nigra. Animals that were co-administered methylphenidate (MPH), a dopamine transport inhibitor, along with the 6-OHDA were spared from the behavioral and neurochemical effects of 6-OHDA, despite receiving more than twice as much neurotoxin as controls. These data suggest that establishing a symptomatic threshold preclinically may help researchers evaluate potential treatments and model individual and group resistance to nigrostriatal insults.
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Comparative Study
Inhibition of morphine analgesia by LPS: role of opioid and NMDA receptors and spinal glia.
Intraperitoneal (i.p.) injection of toxins, such as the bacterial endotoxin lipopolysaccharide (LPS), is associated with a well-characterized increase in sensitivity to painful stimuli (hyperalgesia) [Watkins LR, Maier SF, Goehler LE. Immune activation: the role of pro-inflammatory cytokines in inflammation, illness responses and pathological pain states. Pain 1995;63:289-302. [53]] and a longer-lasting reduction in opioid analgesia (anti-analgesia) when pain sensitivity returns to basal levels [Johnston IN, Westbrook RF. ⋯ Specifically, morphine analgesia was restored if LPS was preceded by systemic administration of a non-competitive NMDA receptor antagonist (MK-801), spinal infusion of a glial metabolic inhibitor (fluorocitrate), or intracerebroventricular microinjection of an opioid receptor antagonist (naloxone). Morphine analgesia was also restored if MK-801 was administered after LPS. These results demonstrate that LPS recruits similar, if not the same mechanisms that reduce morphine tolerance following opiate administration: namely, stimulation of opioid and NMDA receptors and recruitment of spinal glia.
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Clinical Trial Controlled Clinical Trial
Auditory training improves neural timing in the human brainstem.
The auditory brainstem response reflects neural encoding of the acoustic characteristic of a speech syllable with remarkable precision. Some children with learning impairments demonstrate abnormalities in this preconscious measure of neural encoding especially in background noise. This study investigated whether auditory training targeted to remediate perceptually-based learning problems would alter the neural brainstem encoding of the acoustic sound structure of speech in such children. ⋯ However, quiet-to-noise inter-response correlations of the sustained response ( approximately 11-50 ms) increased significantly in the trained children, reflecting improved stimulus encoding precision, whereas control subjects did not exhibit this change. Thus, auditory training can alter the preconscious neural encoding of complex sounds by improving neural synchrony in the auditory brainstem. Additionally, several measures of brainstem response timing were related to changes in cortical physiology, as well as perceptual, academic, and cognitive measures from pre- to post-training.