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  • 1
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science, Ltd
    European journal of neuroscience 16 (2002), S. 0 
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The present study examined the role of the basal forebrain corticopetal cholinergic projection in the regulation of cortical electroencephalographic activity across sleep/wake states in rats. Selective lesions of this projection were effected by local intraparenchymal infusions of the immunotoxin 192 IgG-saporin. Lesions spared the septo-hippocampal cholinergic system, as well as p75-receptor-bearing noncholinergic neurons in the suprachiasmatic nucleus. Relative to sham-lesioned control animals, rats with lesions of basal forebrain cholinergic neurons displayed a significant reduction in high frequency EEG activity, characterized especially by a reduction in gamma EEG power. Lesions did not significantly alter the overall proportion of sleeping and waking states as defined behaviourally, but the attenuation of high frequency EEG activity was apparent across all stages, including REM-like periods. Results are consistent with the view that the basal forebrain corticopetal cholinergic system exerts a general activational effect on the cortical mantle. Although this system may not be essential for sleep/wake stage-switching, it does impact on the cortical states associated with those stages.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 0376-6357
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Psychology
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-2072
    Keywords: Spatial alternation behavior ; Working memory ; Rehearsal ; Scopolamine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rats were trained in an operant spatial delayed alternation task utilizing retention intervals from 2 to 32 s. In addition to response accuracy, operations of the levers during the retention intervals were recorded and analyzed. Animals were tested following the administration of the muscarinic antagonists scopolamine hydrobromide and methylbromide, and the benzodiazepine receptor agonist chlordiazepoxide. In vehicle-treated animals, the relative number of correct responses and correct rehearsal operations (operation of the forthcoming correct lever during retention intervals) varied with the length of the retention intervals, and these measures were correlated. The response rate for rehearsal operations increased with the length of the retention intervals. It is speculated that the delay-dependent increase in response rate reflects an effect of delayed reward that was also associated with a delay-dependent increase in the tendency to alternate between levers. The effects of delay on the accuracy of rehearsal operations may have contributed to the delay-dependent correct responding. Scopolamine hydrobromide (0.01, 0.03, 0.1, 0.3 mg/kg) and methylbromide (0.1, 0.3 mg/kg) impaired correct responding, but did not seem to interfere with the relative number of correct rehearsal operations. As only the presentation of the panel light indicated trial onset, it is speculated that the cholinergic receptor blockade resulted in an increase in the probability of a repositioning response that was triggered by light onset. Chlordiazepoxide (1, 3, 5, 10 mg/kg) did not affect behavioral performance. These results suggest that in tasks that allow the development of rehearsal operations, delay-dependent response accuracy does not represent a sufficient condition for conclusions on task demands on memory. Blockade of peripheral cholinergic receptors may account for the effects of muscarinic antagonists on performance in this task.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-2072
    Keywords: Spatial alteration behavior ; Working memory ; Rehearsal ; Scopolamine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The interactions between the effects of MDL 26,479 (0.1, 0.39, 1.56, 6.25 mg/kg; IP) and the muscarinic antagonist scopolamine (0.03, 0.1 mg/kg; IP) on the performance of rats in a delayed alternation task (retention intervals: 2, 4, 8, 16, 32 s) were examined. Scopolamine dose-dependently reduced the relative number of correct responses and interacted with the effects of the length of retention intervals. MDL 26,479 did not affect correct responding but attenuated the behavioral impairments produced by scopolamine. Although this task did not explicitly exclude the possibility that the animals acquired mediational response strategies, and although the effects of scopolamine appeared to interfere with the execution of these strategies, to a major extent, the attenuative effects of MDL 26,479 were not related to its effects on mediational strategies. Thus, it is concluded that administration of MDL 26,479 mainly resulted in a re-establishment of the animals' ability to memorize and/or to recall the information required to exert correct responses.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 126 (1996), S. 182-184 
    ISSN: 1432-2072
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 118 (1995), S. 195-205 
    ISSN: 1432-2072
    Keywords: Nicotine ; Mecamylamine ; Lobeline ; ABT-418 ; A-82695 ; Attention ; Vigilance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of nicotinic receptor ligands on performance in a task measuring sustained attention, or vigilance, were tested. This task required the animals to discriminate between signal and non-signal events. The sequence of signal (central panel light illumination for 500, 50 or 25 ms) and non-signal presentations was randomized over three blocks of 54 trials each (27 signal trials, 9 per length, and 27 non-signal trials). A left lever press following a signal was counted as a hit, and a right lever press following a non-signal event was counted as a correct rejection. Hits and correct rejections were rewarded, whereas misses and false alarms (defined as incorrect right and left lever presses, respectively) were not. Baseline performance was characterized by a signal length dependent ability of the animals to discriminate between signal and non-signal events. Administration of nicotine (0.19, 0.62, 1.9 µmol) or of two novel nicotinic receptor agonists, ABT-418 and A-82695, did not produce main effects on vigilance performance. Lobeline (1.9, 6.2, 19 µmol), a nicotinic receptor ligand with mixed agonist/antagonist activities, impaired the animals' ability to discriminate between signal and non-signal events. The antagonist mecamylamine (5, 15, 50 µmol) potently impaired performance while increasing the number of errors of omission. The lack of effect of nicotine largely corresponds with the findings from previous studies on the acute effects of nicotine in intact subjects and nonsmoking humans. While the detrimental effects of lobeline may have been related to the antagonist effects of this compound, the reasons for the differences between the effects of nicotine and lobeline still remain unsettled. These data support the hypothesis that nicotine receptor mechanisms are maximally activated in intact animals performing this task, and suggest that effects of acute nicotinic agonist treatment would not produce further cognitive benefit for these animals.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 138 (1998), S. 260-262 
    ISSN: 1432-2072
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-2072
    Keywords: Key words Nicotinic acetylcholine receptor ; ABT-418 ; Methylphenidate ; Basal forebrain ; 192 IgG-saporin ; Sustained attention ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract   Rationale: Loss of telencephalic cholinergic projections has been postulated to contribute significantly to the cognitive decline associated with aging and dementia. Objective: The effects of the nicotinic acetylcholine receptor agonist ABT-418, a potential therapeutic drug for the treatment of the age- and dementia-associated cognitive disorders, were tested in an animal model of the cortical cholinergic deafferentation-induced impairments in sustained attention. Methods: Animals were trained in an operant task designed to test sustained attention performance. A partial loss of cortical cholinergic inputs was produced by infusions of 192 IgG-saporin into the basal forebrain. The effects of the systemic administration of ABT-418 (0.04, 0.13, 0.39 mg/kg) and the psychostimulant methylphenidate (0.2, 0.4, 0.8 mg/kg) were assessed. Results: Compared with sham-lesioned animals, this lesion resulted in a decrease in the relative number of hits while the relative number of correct rejections remained unaffected. Administration of ABT-418 significantly improved the relative number of hits. Furthermore, this effect of ABT-418 interacted with the effects of the lesion. Unexpectedly, this interaction was based on a significant enhancement of the performance of sham-lesioned animals while no effects were found in 192 IgG-saporin-lesioned animals. Administration of methylphenidate did not affect performance. Conclusions: While these data do not support the hypothesis that administration of ABT-418 attenuates the impairments in attentional performance that result from loss of cortical cholinergic inputs, they support previous notions about this drug’s ability to enhance cognitive processes in intact subjects.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1432-2072
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 101 (1990), S. 1-17 
    ISSN: 1432-2072
    Keywords: Basal forebrain ; Acetylcholine ; GABA/benzodiazepine receptor ; ZK 93 426 ; Alzheimer's disease
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The hypothesis that the cognitive decline in senile dementia is related to the loss of cortical cholinergic afferent projections predicts that pharmacological manipulations of the remaining cholinergic neurons will have therapeutic effects. However, treatment with cholinesterase inhibitors or muscarinic agonists has been, for the most part, largely unproductive. These drugs seem to disrupt the normal patterning of cholinergic transmission and thus may block proper signal processing. An alternative pharmacological strategy which focuses on the amplification of presynaptic activity without disrupting the normal patterning of cholinergic transmission appears to be more promising. Such a strategy may make use of the normal GABAergic innervation of basal forebrain cholinergic neurons in general, and in particular of the inhibitory hyperinnervation of remaining cholinergic neurons which may develop under pathological conditions. Disinhibition of the GABAergic control of cholinergic activity is assumed to intensify presynaptic cortical cholinergic activity and to enhance cognitive processing. Although the extent to which compounds such as the benzodiazepine receptor antagonistβ-carboline ZK 93 426 act via the basal forebrain GABA-cholinergic link is not yet clear, the available data suggest that the beneficial behavioral effects of this compound established in animals and humans are based on indirect cholinomimetic mechanisms. It is proposed that an activation of residual basal forebrain cholinergic neurons can be achieved most physiologically via inhibitory modulation of afferent GABAergic transmission. This modulation may have a therapeutic value in treating behavioral syndromes associated with cortical cholinergic denervation.
    Type of Medium: Electronic Resource
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