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

Wagner, H. N.; Dannals, R. F.; Links, Jonathan M.; Frost, J. James; Ravert, Hayden T.; Wilson, Alan A.; Rosenbaum, A. E.; Gjedde, Albert; Douglass, Kenneth H.; Petronis, J. D.; Folstein, M. F.; Toung, J. K.; Burns, H. Donald; Kuhar, Michael J.; Wong, Dean F.

doi:10.1097/00004728-198505000-00081

Cited by 138 publications

(176 citation statements)

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“…Consistent with animal and human postmortem studies documenting serotonin subtype-2 (5-HT) recep tors in frontal cortex, Wong et al (1984) documented in vivo 5-HT2 receptor uptake in human frontal cortex using positron-emission tomography (PET) and llC-N methylspiperone. Using PET and 18-fluorodeoxyglu cose, Benkelfat et al (1989) found that the serotonergic drug, clomipramine, reduced abnormally high values of regional cerebral metabolic rate of glucose (rCMRG) in the orbital frontal cortex of patients with obsessive compulsive disorder.…”

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confidence: 54%

Positron-Emission Tomography and Personality Disorders

Pj²,

et al. 1994

Neuropsychopharmacol

228

104

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This study used positron-emission tomography to examine cerebral metabolic rates of glucose (CMRG) in 17 patients with DSM III-R diagnoses of personality disorder. Within the group of 17 personality disorder patients, there was a significant inverse correlation between a life history of aggressive impulse difficulties and regional CMRG in the frontal cortex of the transaxial plane approximately 40 mm above the canthomeatal line (CML) (r = -.56, P = 0.17). Diagnostic groups included antisocial (n = 6), borderline (n = 6), dependent (n = 2), and narcissistic (n = 3).KEY WORDS: Positron-emission tomography; Cerebral glucose metabolism; Personality disorder; Borderline personality disorder; Antisocial personality disorder; Regional cerebral metabolic rate of glucose Cerebrospinal fluid (CSF) 5-hydroxyindoleacetic acid (5-HIAA) has been shown to inversely correlate with a life history of aggressive impulse diffIculties in patients with personality disorder diagnoses (Brown et al. 1979). This initial study examined 26 patients from nine differ ent personality disorder diagnostic groups. A subse-

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confidence: 54%

Positron-Emission Tomography and Personality Disorders

Pj²,

et al. 1994

Neuropsychopharmacol

228

104

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“…Although striatal DA D2 receptor availability declines with age (eg Wong et al, 1984Wong et al, , 1997Rinne et al, 1993;Mukherjee et al, 2002), it is unlikely that age served as a confounding variable in this study. The average age of the monkeys was approximately 13, with a range of 9-17 years old.…”

Section: Discussionmentioning

confidence: 88%

Effect of Menstrual Cycle Phase on Dopamine D2 Receptor Availability in Female Cynomolgus Monkeys

Czoty

Riddick

Gage

et al. 2008

Neuropsychopharmacol

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Sex differences have been reported in a variety of affective and neurodegenerative disorders that involve dysfunctional dopamine (DA) neurotransmission. In addition, there is evidence for differences in sensitivity to the abuse-related effects of psychostimulants across the menstrual cycle which may result from effects of ovarian hormones on DA function. The goal of the present study was to extend previous work examining menstrual cycle-related changes in DA D2 receptor availability in humans to drug-naive female cynomolgus monkeys (n ¼ 7) using the selective D2-like receptor ligand [ 18 F]fluoroclebopride (FCP) and a high-resolution microPET P4 scanner. Menstrual cycle phase was characterized by daily vaginal swabs and measurements of serum progesterone levels. PET studies were conducted once during the luteal phase and once during the follicular phase. Regions of interest in the caudate nucleus, putamen, and cerebellum were defined on coregistered MRIs. Distribution volumes were calculated for FCP in each structure and the distribution volume ratio (DVR) for both brain regions relative to the cerebellum was used as a measure of D2 receptor availability. FCP DVRs were significantly higher in the luteal phase compared to the follicular phase in both the caudate nucleus (11.7% difference, p ¼ 0.02) and putamen (11.6% difference, p ¼ 0.03). These findings extend earlier work in humans and suggest that changes in DA receptor availability may be involved in the variation in symptoms of various neuropsychiatric disorders across the menstrual cycle, including differences in sensitivity to the abuse-related effects of stimulants.

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“…Indeed, the studies of Wong et al (1984) provided the initial interest to address this problem in a more formal manner. For example, it has been shown that re ceptors for specific neurotransmitters are absent or have much lower affinity for the test ligand in cer tain brain structures and that the time course of tissue radioactivity in different structures can be compared after the administration of particular ra diolabeled ligands.…”

Section: Specific Applicationsmentioning

confidence: 99%

Graphical Evaluation of Blood-to-Brain Transfer Constants from Multiple-Time Uptake Data. Generalizations

Patlak

Blasberg

1985

J Cereb Blood Flow Metab

1,477

725

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Summary:The method of graphical analysis for the eval uation of sequential data (e.g., tissue and blood concen trations over time) in which the test substance is irre versibly trapped in the system has been expanded. A sim pler derivation of the original analysis is presented.General equations are derived that can be used to analyze tissue uptake data when the blood-plasma concentration of the test substance cannot be easily measured. In ad dition, general equations are derived for situations when trapping of the test substance is incomplete and for a combination of these two conditions. These derivationsThe study of the movement of solute molecules across tissue capillaries and their localization within selected tissues of both animal and human subjects has been greatly facilitated by the use of tomo graphic machines. These instruments can provide sequential measurements over time of regional tissue concentrations. The general experimental protocol usually involves the injection of the test substance into the blood of the subject and then measuring the concentration of the substance in both the blood and various tissue regions over a period of time. These data may then be analyzed by a number of methods to ascertain the desired parameters of the system.One method of analysis that has been proposed for those substances that are irreversibly trapped in the system is a graphical analysis of multiple time data points . For this method, an equation has been developed for a very general model. When certain measurable quantities are This approach is also shown to result in equations with at least one less nonlinear term than those derived from direct compartmental analysis. Specific applications of these equations are illustrated for a compartmental system with one reversible region (with or without re versible binding) and one irreversible region.

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

Cited by 138 publications

References 0 publications

Positron-Emission Tomography and Personality Disorders

Positron-Emission Tomography and Personality Disorders

Effect of Menstrual Cycle Phase on Dopamine D2 Receptor Availability in Female Cynomolgus Monkeys

Graphical Evaluation of Blood-to-Brain Transfer Constants from Multiple-Time Uptake Data. Generalizations

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