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  • 1
    ISSN: 1432-2072
    Keywords: Delayed alternation ; Spatial memory ; Cortex ; Dopamine ; Noradrenaline ; 5-Hydroxytryptamine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Seventeen male Sprague-Dawley rats were trained to eight to nine correct responses on a delayed spatial alternation test performed on alternate days in a T-maze. Locomotor activity in an observation box was scored on 2 consecutive days. The animals were killed 2 weeks after the end of behavioural testing and dopamine (DA), noradrenaline (NA), 5-hydroxytryptamine (5HT), the DA metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) and the 5HT metabolite, 5-hydroxyindoleacetic acid (5HIAA) determined in cortex, hippocampus, striatum and hypothalamus. Cortical concentrations of both DA and NA correlated negatively and significantly with the number of errors made in learning the alternation task, though the latter correlation was less striking and became negligible after the correlation between DA and NA was partialled out. Concentrations of DA and NA in the other regions did not correlate significantly with errors. None of the other neurochemical variables correlated significantly with either errors or locomotor activity, except for hypothalamic HVA concentration which showed a marginally significant correlation with locomotor activity. The above results, together with effects of brain lesions reported by other authors, strongly indicate that cortical catecholamines facilitate learning in the normal non-drug-treated rat.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-2072
    Keywords: Key words Noradrenaline ; Locus coeruleus ; Cognition ; Clonidine ; Idazoxan ; Imidazoline
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Several investigations have revealed substantial influences of pharmacological manipulation of central noradrenergic activity upon performance in cognitive tests sensitive to frontal lobe dysfunction. They suggest a significant role for the noradrenergic coeruleo-cortical projection in cognitive function but conflicting findings and the complex pharmacology of adrenoceptor agents make it difficult to be precise about underlying mechanisms. In order to clarify these we have compared the effects of an α1/α2-adrenoceptor agonist, clonidine, an α2-adrenoceptor antagonist, idazoxan, and these agents in combination. Three groups of healthy volunteers were used to investigate the effects of these noradrenergic manipulations upon performance of tasks from the CANTAB test battery known to be sensitive to frontal lobe dysfunction. Previously reported effects of clonidine upon sustained visual attention and upon session-to-session improvement were replicated. Furthermore, idazoxan inhibited the hypotensive effect of clonidine. Idazoxan had no overall effect on performance of any of the tests but did inhibit session-to-session improvement in performance of a planning task, attentional set shifting and sustained visual attention. Rather than leading to the anticipated mutual antagonism of effects, combining clonidine and idazoxan led to a wider and more striking range of cognitive impairments. These results are discussed alongside findings which support a role for imidazoline (I1) receptors in blood pressure control, where clonidine and idazoxan are antagonistic, and evidence of less potent antagonism at somato-dendritic α2-adrenoceptors in the locus coeruleus.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-2072
    Keywords: Key words Catecholamine ; 5-Hydroxytryptamine ; Attentional control ; Stimulus-reward learning ; Prefrontal cortex (PFC) ; Impulsivity ; Distractibility
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: Altered serotonergic and dopaminergic function have been widely implicated in behavioural disorders associated with impulsivity and risk-taking. However, little research has addressed the specific cognitive consequences of changed monoaminergic function that might contribute to the production of impulsive behaviour. Objectives and methods: We compared the effects of rapid plasma tryptophan depletion, acute doses of the mixed indirect catecholamine agonist, methylphenidate (40 mg), and acute doses of the α1/α2 agonist, clonidine (1.5 µg/kg), on aspects of visual discrimination learning involving either acquisition of altered stimulus-reward associations (i.e. updating the affective valence of exteroceptive stimuli) or the control of attention towards relevant as opposed to irrelevant stimulus dimensions. Results: Relative to subjects who received placebo, subjects with reduced tryptophan exhibited a deficit in the ability to learn changed stimulus-reward associations, but were still able to shift an acquired attentional set away from a now-irrelevant stimulus dimension towards a newly relevant dimension. By contrast, subjects who received methylphenidate were able to learn effectively about changing stimulus-reward associations, but showed an enhanced ability to shift an attentional bias, in combination with slowed response times. Subjects who received clonidine showed neither of these changes. Conclusions: These results suggest that reduction in central serotonin leads to altered neuromodulation of the cortical and subcortical regions (e.g. orbitofrontal cortex, striatum and anterior temporal structures) that mediate important aspects of associative learning whereby exteroceptive stimuli acquire altered incentive motivational value. On the other hand, facilitation of catecholamine neurotransmitters may disrupt the allocation of attention between relevant and irrelevant features of the environment, perhaps through altered modulation of the dorsolateral prefrontal cortex. The implications of these results for understanding the differential neuromodulation of cognitive functions are discussed.
    Type of Medium: Electronic Resource
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