Effects of Age on Dopamine and Serotonin Receptors Measured by Positron Tomography in the Living Human Brain

Wong, Dean F.; Wagner, Henry N.; Dannals, Robert F.; Links, Jonathan M.; Frost, J. James; Ravert, Hayden T.; Wilson, Alan A.; Rosenbaum, Arthur E.; Gjedde, Albert; Douglass, Kenneth H.

doi:10.1126/science.6334363

Cited by 650 publications

(87 citation statements)

References 63 publications

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“…Secondly, data obtained using autoradiographic techniques, unlike PET, necessitate the use of postmortem material and thus are inherently subject to alterations due to tissue autolysis resulting perhaps, in an underestimation in receptor number (Brady and Mufson, 1990). The magnitude of the decrease in muscarinic cholinergic receptor binding observed in this study is consistent with that observed in the dopaminergic D, receptor system in male subjects using L"C1-3-N-methylspiperone and PET (Wong, et al, 1984). As only male volunteers were used in this study, we are unable to establish whether or not there are sex differences in [N-C-methyl]-benztropine binding similar to those reported by Wong and his colleagues.…”

Section: Discussionsupporting

confidence: 87%

“…With the development of selective radiolabelled tracers for different neurotransmitter systems, advances have been made in understanding both the underlying pathophysiology of some neurotransmitter-specific central nervous system (CNS) diseases (Wong, et al, 1986;Frost, et al, 1988;Lucignani, et al, 1990) as well as interactions occurring between one neurotransmitter system (muscarinic cholinergic) and another (dopaminergic) (Dewey, et al, 1988;1990a,b). PET studies designed to examine the effects of aging on the dopaniinergic D, and serotonergic receptor system have also been reported (Wong, et al, 1984).…”

Section: Introductionmentioning

confidence: 98%

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Age‐related decreases in muscarinic cholinergic receptor binding in the human brain measured with positron emission tomography (PET)

Dewey

Volkow

Logan

et al. 1990

J of Neuroscience Research

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Muscarinic cholinergic M1 and M2 receptors in young and aged adult male volunteers were studied using [N-11C-methyl]-benztropine, a specific muscarinic cholinergic receptor ligand, and high resolution positron emission tomography (PET). A regionally specific pattern of decreased binding was observed in aged volunteers. Using two separate methods of data analysis, thalamic, hippocampal and cerebellar regions showed no decreases in the apparent specific binding of [N-11C-methyl]-benztropine while frontal, parietal, temporal and occipital cortices as well as the corpus striatum showed age related changes in binding that declined (in 82 yrs old subject) to about 50% of the value obtained from the youngest volunteer (19 yrs). These data suggest that regions high in muscarinic receptor density, the corpus striatum and the cortical mantle, show a greater rate of decline than those areas that have a relatively low number of muscarinic receptors. Furthermore, this study demonstrates the usefulness of PET and [N-11C-methyl]-benztropine for assessing age related regional changes in muscarinic cholinergic receptor binding in the living human brain.

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Section: Discussionsupporting

confidence: 87%

Section: Introductionmentioning

confidence: 98%

Age‐related decreases in muscarinic cholinergic receptor binding in the human brain measured with positron emission tomography (PET)

Dewey

Volkow

Logan

et al. 1990

J of Neuroscience Research

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“…Under such conditions, the binding potential in target regions cannot be determined as a k3/k4 ratio from a compartment model, since k4 is extremely small and not significantly different from zero. It can be shown that for time intervals T >> 1/k2 and if k3 << k2, the target/nontarget ratio (B/F) of an irreversible antagonist will increase in the following way [29,30]:…”

Section: Methodsmentioning

confidence: 99%

Measuring Receptor Occupancy with PET

Waarde¹

2000

CPD

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Many physiological and biochemical measurements can be performed noninvasively in humans with modern imaging techniques like magnetic resonance imaging (MRI), positron emission tomography (PET) or single-photon emission computed tomography (SPECT). This review focuses on the monitoring of drug-receptor interactions in patients and healthy volunteers with PET. Such studies depend on the availability of a suitable radioligand; they are already possible for classical and atypical neuroleptics, anxiolytics, antidepressants, anticholinergics, antihistamines, antiepileptics, beta-blockers and hypnotic drugs. In Phase I-II human studies, measurements of plasma pharmacokinetics can be combined with images of receptor occupancy and be quantitatively related to pharmacologic effects which are induced in the same subjects. Optimal dosing schedules can be defined and valuable information for the design of Phase III studies can be acquired. Moreover, the effect of interventions (e.g. change of dose, additional medication) can be predicted. Medical imaging techniques will play an increasing role in clinical pharmacology and allow well-informed go/no-go decisions in future drug development.

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“…Throughout the human life span (18 to 73 years) the density of D2-like neuroreceptors in the caudate nucleus, the putamen, and the frontal cerebral cortex is inversely proportional to the age of the person [31] .…”

Section: D2-like Neuroreceptor Imaging Throughout the Lifespanmentioning

confidence: 99%

“…Serotonin 5-HT 2A receptors [ 11 C]NMSP was utilized to estimate the density and the distribution of cortical serotonin 5-HT 2A and striatal dopamine D2-like neuroreceptors in people with schizophrenia [31] . Reductions in the density of prefrontal cortical 5-HT 2A receptors have been demonstrated in some drug-naïve people with schizophrenia to confirm autopsy studies [11] .…”

Section: Imaging Serotonin Receptors In the Brain Of People With Schimentioning

confidence: 99%

Neurotransmitter visualization in schizophrenia

Brašić

2013

JBGC

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Background: Although the history, interview, and examination of the patient provide the foundation for the diagnosis of schizophrenia, nuclear neuroimaging investigations constitute promising tools to elucidate the pathophysiology of schizophrenia and other neuropsychiatric disorders. Imaging studies of neuroreceptors constitute research tools to investigate the role of dysfunction of the acetylcholinergic, dopaminergic, glutamatergic, serotonergic, cannabinoid, opioid, and nicotinic systems in the pathogenesis and pathophysiology of schizophrenia and related conditions.People with the phenotype of the clinical syndrome of schizophrenia likely represent multiple distinct genotypes with poorly characterized biological traits. Thus, the population of people manifesting the clinical syndrome of schizophrenia likely contains several heterogeneous biological subgroups yet to be specified.The dopamine hypothesis of schizophrenia proposes that the positive symptoms result from an excess of intrasynaptic dopamine, an excitatory neurotransmitter, and the negative symptoms result from a deficit of intrasynaptic dopamine. Accordingly, a group of people with schizophrenia likely have reduced intrasynaptic dopamine in the tonic, resting, basal state, and increased intrasynaptic dopamine in the excited, aroused, phasic state.Additionally, the glutamate hypothesis of schizophrenia suggests that dysfunction of glutamate, another excitatory neurotransmitter, in the prefrontal region results in excessive concentrations of dopamine in the striata resulting in the positive symptoms of schizophrenia. Methodology/Principal Findings:Published research about the nuclear neuroimaging techniques to identify neurotransmitters in people with schizophrenia are reviewed.Conclusions/Significance: Future research including neuronuclear imaging and genetic evaluations is needed to characterize the biological subgroups of people with the clinical syndrome of schizophrenia. Neuronuclear imaging studies will likely refine the measurement of neurotransmitters in the presynaptic, synaptic, and postsynaptic regions in people with schizophrenia and healthy people. Imaging studies of neuroreceptors during the administration of putative therapeutic agents for schizophrenia will help determine the optimal dose. In the future the research findings summarized in this article will likely be translated into clinical practice.

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Effects of Age on Dopamine and Serotonin Receptors Measured by Positron Tomography in the Living Human Brain

Cited by 650 publications

References 63 publications

Age‐related decreases in muscarinic cholinergic receptor binding in the human brain measured with positron emission tomography (PET)

Age‐related decreases in muscarinic cholinergic receptor binding in the human brain measured with positron emission tomography (PET)

Measuring Receptor Occupancy with PET

Neurotransmitter visualization in schizophrenia

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