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  • 1
    Electronic Resource
    Electronic Resource
    The Effect of Apomorphine and Buspirone on Regional Cerebral Blood Flow During the Performance of a Cognitive Task—Measuring Neuromodulatory Effects of Psychotropic Drugs in Man (1992)
    Oxford, UK : Blackwell Publishing Ltd
    European journal of neuroscience 4 (1992), S. 0 
    Details
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Psychopharmacological activation, in conjunction with positron emission tomographic measurements of regional cerebral blood flow (rCBF), was used to investigate the neurotransmitter basis of a specific cognitive function in man. Monoaminergic neurotransmission was pharmacologically manipulated during performance of auditory – verbal memory tasks. Statistical parametric mapping was used to identify the brain sites of interaction between memory-induced increases in rCBF and active drugs. Memory task-induced increases in rCBF in the left prefrontal cortex were attenuated by apomorphine, a non-selective dopamine agonist, whilst buspirone, a serotonin1A partial agonist, augmented rCBF increases in this area. In addition, apomorphine and buspirone augmented memory-induced increases in rCBF centred in the posterior cingulate cortex, whilst buspirone alone attenuated rCBF increases in the retrosplenial cortex and posterior parahippocampal gyrus. These regionally selective interactions may represent neuromodulatory effects of monoaminergic neurotransmission on a specific cognitive function in man.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1460-9568.1992.tb00145.x
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  • 2
    Electronic Resource
    Electronic Resource
    The Neural Correlates of the Noradrenergic Modulation of Human Attention, Arousal and Learning (1997)
    Oxford, UK : Blackwell Publishing Ltd
    European journal of neuroscience 9 (1997), S. 0 
    Details
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The prefrontal cortex has been suggested as a site of action for the noradrenergic modulation of cognition. In healthy volunteers attentional deficits can be induced by the α2 adrenoceptor agonist clonidine, without impairment of more explicit tests of frontal lobe function. It is therefore possible that the effects of noradrenaline cannot be localized to a specific brain area such as the prefrontal cortex, but instead involve structures in a more widespread attentional network. A 1.5 μg/kg dose of clonidine or placebo was administered to 13 healthy male volunteers performing the rapid visual information processing task, which places demands on both sustained attention and working memory. Twelve positron emission tomography measurements of regional cerebral blood flow (rCBF) were collected during performance of this task and also during a rest state. A second experiment in 12 healthy volunteers examined the effects of a 1.3 μg/kg dose of clonidine on the rCBF changes associated with performance of a paired associates learning task compared with passive listening to word pairs. Comparison of each of the experimental tasks with its respective control replicated previous findings. A significant drug × task interaction, common to the two studies, was found in the right thalamus. Inspection of the adjusted rCBF values showed that the effect was due to attenuation of thalamic rCBF during the control states rather than to any effects of clonidine during performance of the cognitive tasks, although the effect was stronger in the rapid visual information processing study than in the paired associates learning study. The significant effect of clonidine during the control as opposed to the ‘cognitive’ activation state is consistent with previous findings in animals and humans demonstrating greater effects of clonidine during states of relatively low arousal. The results suggest neuroanatomical dissociation of the noradrenergic modulation of arousal (via the thalamus) and attention.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1460-9568.1997.tb01635.x
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  • 3
    Electronic Resource
    Electronic Resource
    Dopaminergic modulation of impaired cognitive activation in the anterior cingulate cortex in schizophrenia (1995)
    [s.l.] : Nature Publishing Group
    Nature 378 (1995), S. 180-182 
    Details
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] We measured brain activity, indexed by regional cerebral blood flow (rCBF), in 12 normal male volunteer subjects and 12 unmedicated male schizophrenic patients under two conditions. We scanned all subjects while they performed a paced verbal fluency task and a baseline paced verbal repetition task ...
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1038/378180a0
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  • 4
    Electronic Resource
    Electronic Resource
    Evidence for striatal dopamine release during a video game (1998)
    [s.l.] : Macmillan Magazines Ltd.
    Nature 393 (1998), S. 266-268 
    Details
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] Dopaminergic neurotransmission may be involved in learning, reinforcement of behaviour, attention, and sensorimotor integration,. Binding of the radioligand 11C-labelled raclopride to dopamine D2 receptors is sensitive to levels of endogenous dopamine, which can be ...
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1038/30498
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  • 5
    Electronic Resource
    Electronic Resource
    Effects of the 5-HT1A partial agonists gepirone, ipsapirone and buspirone on local cerebral glucose utilization in the conscious rat (1992)
    Springer
    Psychopharmacology 106 (1992), S. 97-101 
    Details
    ISSN: 1432-2072
    Keywords: Gepirone ; Buspirone ; Ipsapirone ; Glucose utilization ; Hippocampus ; Lateral habenular nucleus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The azospirones gepirone (10 mg/kg), ipsapirone (10 mg/kg) and buspirone (10 mg/kg) were examined for their effect on regional cerebral glucose utilization in conscious rats using quantitative 2-deoxyglucose autoradiography. All three 5-HT1A partial agonists reduced glucose utilization in the hippocampus and dentate gyrus by 20–25% and increased glucose utilization by 38–65% in the lateral habenular nucleus; an important relay between striatal/limbic areas and the mid-brain raphe nuclei. The findings emphasize the potential importance of the hippocampus as a site of action for 5-HT1A receptor active drugs in vivo and also suggest that functional activity in the striatal/limbichabenular-raphe pathway may be influenced by gepirone, ipsapirone and buspirone.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02253595
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  • 6
    Electronic Resource
    Electronic Resource
    The time course of binding to striatal dopamine D2 receptors by the neuroleptic ziprasidone (CP-88,059-01) determined by positron emission tomography (1996)
    Springer
    Psychopharmacology 124 (1996), S. 141-147 
    Details
    ISSN: 1432-2072
    Keywords: Positron emission tomography ; Pharmacokinetics ; 11C-Raclopride ; Dopamine D2 receptors ; Ziprasidone ; CP-88,059-1
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Positron emission tomography (PET) and11C-raclopride were used to assess the time course of binding to central dopamine D2 receptors by the novel neuroleptic ziprasidone. In a third party blind study, six healthy male control subjects received a predose of 40 mg ziprasidone and were scanned at an interval of between 4 and 36 h post-dose. One additional subject was assigned to placebo predose and was scanned at 4 h post-dose. Binding potential (BP) was compared with that seen in the subject predosed with placebo and with that seen in nine unmedicated normal volunteers. Subjects studied up to 12 h post-dose had BPs that were greater than 2 SD less than the mean BP, indicative of extensive D2 receptor binding by ziprasidone. With increasing time between dosing and PET scanning there was a curvilinear increase in BP, so that all studies performed at or after 18 h post-dose gave BPs in the normal range (mean±2 SD). Elevated prolactin levels returned to within the normal range by 18 h post-dose. PET measures of binding potential correlated significantly with serum levels of ziprasidone at the time of scanning and less significantly with absolute prolactin levels at the same time.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02245614
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  • 7
    Electronic Resource
    Electronic Resource
    The effect of the muscarinic antagonist scopolamine on regional cerebral blood flow during the performance of a memory task (1995)
    Springer
    Experimental brain research 104 (1995), S. 337-348 
    Details
    ISSN: 1432-1106
    Keywords: Scopolamine ; Memory ; Positron emission tomography ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Scopolamine, a muscarinic antagonist, impairs memory performance in both humans and animals. In this study, repeated measurements of regional cerebral blood flow (rCBF) were made in normal volunteers whilst performing auditory verbal memory tasks, before and after the administration of scopolamine (0.4 mg s.c.) or placebo. Compared to placebo, scopolamine increased blood flow in the lateral occipital cortex bilaterally and the left orbitofrontal region. Scopolamine decreased rCBF in the region of the right thalamus, the precuneus and the right and left lateral premotor areas. Scopolamine attenuated memory-task-induced increases of rCBF in the left and right prefrontal cortex and the right anterior cingulate region. These data suggest that acute blockade of cholinergic neurotransmission affects diverse brain areas, including components of the visual and motor systems, and, in addition, modulates memory task activations at distinct points in a distributed network for memory function.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00242019
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  • 8
    Electronic Resource
    Electronic Resource
    Dose dependent occupancy of central dopamine D2 receptors by the novel neuroleptic CP-88,059-01: a study using positron emission tomography and11C-raclopride (1993)
    Springer
    Psychopharmacology 112 (1993), S. 308-314 
    Details
    ISSN: 1432-2072
    Keywords: Positron emission tomography ; Pharmacodynamics ; 11C-raclopride ; Dopamine D2 receptors ; CP-88,059-1
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Positron emission tomography (PET) and11C-raclopride were used to measure the occupancy of central dopamine D2 receptors by a new neuroleptic, CP-88,059-1. In a double blind dose escalation study, seven healthy male subjects received a predose of between 2 mg and 60 mg CP-88,059-1, 5 h before PET scanning. One additional subject was assigned to placebo predose. Receptor occupancy was defined as the percentage reduction in binding potential compared with that seen in the subject predosed with placebo and with that seen in seven unmedicated normal volunteers previously studied. Binding of11C-raclopride decreased in a dose dependent manner, and 85% dopamine D2 receptor occupancy was achieved with the highest dose of CP-88,059-1. The findings confirm that brain dopamine D2 receptors are blocked by CP-88,059-1 and suggest that an effective antipsychotic dose will be between 20 mg and 40 mg. The study highlights the potential of positron emission tomography in the preclinical evaluation of new drugs.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02244926
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  • 9
    Electronic Resource
    Electronic Resource
    Effect of the 5-HT1A partial agonist buspirone on regional cerebral blood flow in man (1992)
    Springer
    Psychopharmacology 108 (1992), S. 380-386 
    Details
    ISSN: 1432-2072
    Keywords: Buspirone ; 5-HT1A receptors ; Positron emission tomography ; Statistical parametric mapping ; Pharmacological challenge
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Repeated measurements of regional cerebral blood flow (rCBF) were made in normal volunteers before, and after, the administration of the 5-HT1A partial agonist, buspirone, or placebo. The difference in rCBF, before and after drug, (buspirone versus placebo) was used to identify brain areas affected by buspirone. Buspirone-induced changes in rCBF were studied under two behavioural conditions (5 word-list learning and 15 word-list learning). Compared to placebo, buspirone increased blood flow in the cuneus during both behavioural states. However, decreases in blood flow, centred in the left dorso-lateral prefrontal cortex and posterior cingulate cortex, were only observed under one of the two behavioural conditions. It is concluded that buspirone-induced alterations in regional cerebral blood flow are better understood, not in relation to the known distribution of monoamine neurotransmitter systems (particularly ascending 5-HT projections), but rather in relation to putative neuronal circuits possibly many synapses “downstream” of buspirone's pharmacological site of action.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02245127
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