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Query: UMLS:C0085632 (apathy)
 4,089 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We describe 2 new patients from a family in which 10 persons in 3 successive generations had a dominant neuropsychiatric disorder characterized by apathy, central hypoventilation, and parkinsonism. Neuropathologically, both patients showed severe neuronal loss and reactive gliosis in the substantia nigra. Neurochemical studies showed a marked depletion of dopamine in substantia nigra, putamen, and caudate nucleus, as well as reduction in serotonin content in the substantia nigra. Glutamate contents were low in frontal cortex and thalamus, and gamma-aminobutyric acid (GABA) contents were low in thalamus and substantia nigra of both patients. In addition, phosphoethanolamine contents were reduced in all brain regions of both patients, especially in the substantia nigra. One patient with severe symptoms had low levels of homovanillic acid, 5-hydroxyindoleacetic acid, and GABA in his CSF repeatedly for 3 years before death (aged 58), while the 2nd patient died (aged 51) of an unrelated cause before developing any symptoms of the familial disorder. Because brain deficiencies of multiple neurotransmitters appear to be involved, this disorder is unlikely to respond to treatment; however, neurochemical studies of CSF may make presymptomatic diagnosis feasible.
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PMID:Dominantly inherited apathy, central hypoventilation, and Parkinson's syndrome: clinical, biochemical, and neuropathologic studies of 2 new cases. 224 38

The possible involvement of the ascending 5-hydroxytryptaminergic (5HTergic) pathways in determining the effectiveness of delayed positive reinforcers was investigated using Mazur's (1984) adjusting-delay paradigm. Fourteen rats received injections of 5,7-dihydroxytryptamine into the dorsal and median raphe nuclei; 12 rats received sham lesions. The rats made repeated choices in a two-lever operant conditioning chamber between a smaller reinforcer delivered after a 2-s delay and a larger reinforcer delivered after a variable delay, the length of which was determined by the subject's previous choices. When the two reinforcers consisted of one and two food pellets, the "indifference point" (the delay to the larger reinforcer that rendered the two reinforcers equally effective) was shorter in the lesioned group than in the control group. Increasing the sizes of the reinforcers to three and six pellets reduced the indifference point in both groups and abolished the between-group difference. The levels of 5HT and 5-hydroxyindoleacetic acid (5HIAA) in the parietal cortex, hippocampus, amygdala, nucleus accumbens and hypothalamus were greatly reduced in the lesioned group, but the levels of noradrenaline and dopamine were not significantly affected. The results are consistent with the suggestion that the 5HTergic pathways play a role in maintaining the effectiveness of delayed reinforcers.
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PMID:Effect of lesions of the ascending 5-hydroxytryptaminergic pathways on choice between delayed reinforcers. 787 Sep 58

This experiment examined the effect of destruction of the ascending 5-hydroxytryptaminergic (5HTergic) pathways on performance in a free-operant timing schedule. Rats received either injections of 5,7-dihydroxytryptamine into the dorsal and median raphe nuclei or sham lesions. They were trained to press levers for a sucrose reinforcer. Training sessions consisted of 40, 50-s trials in which reinforcers were available on a variable-interval 25-s schedule; in the first 25 s of each trial, reinforcers were only available for responses on lever A, whereas in the last 25 s reinforcers were available only for responses on lever B. Data were collected from probe trials (four per session) in which no reinforcers were delivered, during the last ten of 50 training sessions. Both groups showed decreasing response rates on lever A and increasing response rates on lever B as a function of time from the onset of the trial. Response rate on lever B, expressed as a percentage of overall response rate, could be described by a two-parameter logistic function; neither the indifference point (i.e. the time corresponding to 50% responding on lever B) nor the slope of the function different between the two groups. However, the lesioned group showed a higher rate of switching between response alternatives than the sham-lesioned group. The levels of 5HT and 5-hydroxyindoleacetic acid were reduced in the brains of the lesioned rats, but the levels of noradrenaline and dopamine were not significantly altered. The results confirm previous findings that behaviour in timing schedules is sensitive to destruction of the central 5HTergic pathways, and suggest that these pathways may contribute to the inhibitory regulation of switching between behavioural states.
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PMID:Effect of destruction of the 5-hydroxytryptaminergic pathways on behavioural timing and "switching" in a free-operant psychophysical procedure. 892 70

This experiment examined the effect of destroying central noradrenergic neurones, using the selective neurotoxin DSP4 [N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine], on performance in a free-operant timing schedule. Rats received either systemic treatment with DSP4 or vehicle-alone injections. They were trained to press levers for a sucrose reinforcer. Training sessions consisted of 40, 50-s trials in which reinforcers were available on a variable-interval 25-s schedule; in the first 25 s of each trial, reinforcers were only available for responses on lever A, whereas in the last 25 s reinforcers were available only for responses on lever B. Data were collected from probe trials (four per session), in which no reinforcers were delivered, during the last ten of 60 training sessions. Both groups showed decreasing response rates on lever A, and increasing response rates on lever B, as a function of time from the onset of the trial. Quantitative indices of timing behaviour were derived from a two-parameter logistic function fitted to the relative response rates on lever B (response rate on lever B, expressed as a percentage of overall response rate); this function accounted for > 90% of the data variance in each group. The DSP4-treated group showed a significantly lower value of the indifference point (i.e. the time corresponding to 50% responding on lever B) than the control group. The slope of the function and the rate of switching between response alternatives did not differ significantly between the two groups. The concentrations of noradrenaline were markedly reduced in the neocortex and hippocampus of the DSP4-treated group, but the concentrations of dopamine, 5-hydroxytryptamine and 5-hydroxyindoleacetic acid were not significantly altered. It is suggested that results may be consistent with a role of the dorsal ascending noradrenergic pathway in behavioural "arousal".
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PMID:Effect of destruction of noradrenergic neurones with DSP4 on performance on a free-operant timing schedule. 956 8

This experiment examined the effect of destroying the ascending 5-hydroxytryptaminergic (5-HTergic) pathways on timing and switching behaviour in the free-operant psychophysical procedure. Rats received injections of 5,7-dihydroxytryptamine into the dorsal and median raphe nuclei or sham lesions. They were trained to press levers for sucrose reinforcement; sessions consisted of fifty 50-s trials in which reinforcers were available on a variable-interval 30-s schedule. In the first 25 s, of each trial, reinforcement was only available for responses on lever A; in the last 25 s, it was available only for responses on lever B. In phase 1 (70 sessions) repetitive switching between the levers was prevented by withdrawal of lever A after the first response on lever B in each trial; in phase 2 (40 sessions) this constraint on switching was removed; in phase 3 (40 sessions) the constraint was reinstated. Data were collected from probe trials (four per session) in which no reinforcers were delivered, during the last ten sessions of each phase. In all phases, both groups showed declining response rates on lever A and increasing response rates on lever B as a function of time from the onset of the trial. Response rate on lever B, expressed as percentage of overall response rate, could be described by a two-parameter logistic function. Removal of the constraint on switching reduced the slope of the function without changing the indifference point (time corresponding to 50% responding on lever B). The parameters of the timing function did not differ between the groups in any of the phases. However, the lesioned group showed a greater enhancement of switching rate during phase 2 than the control group. The levels of 5-HT and 5-hydroxyindoleacetic acid were reduced in the brains of the lesioned rats, but the levels of noradrenaline and dopamine were not altered. The results provide further evidence for the involvement of the ascending 5-HTergic pathways in switching between response alternatives, but cast doubt on our previous suggestion that the effects of 5-HT depletion on temporal differentiation of behaviour are mediated by facilitated switching.
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PMID:Effect of central 5-hydroxytryptamine depletion on performance in the free-operant psychophysical procedure: facilitation of switching, but no effect on temporal differentiation of responding. 1032 79