Biomedical subjects

J Booij

Publications and source records attributed to J Booij.

At least 19 recordsLinked to original sources

PubMed2002

[Presymptomatic detection of Parkinson's disease].

Parkinson's disease (PD) is characterized by a progressive degeneration of mesencephalic dopaminergic neurons. More than half of these neurons are lost in a presymptomatic phase of an estimated 4-6 years duration. It is obvious that any type of treatment aimed at slowing down the disease process should preferably be applied in this presymptomatic phase. Presymptomatic detection of PD has therefore become an important goal. In a recent study in a population of 361 asymptomatic first degree relatives of PD patients, we were able to demonstrate that presymptomatic detection is possible by means of a combination of three olfactory processing tasks and [123l] beta-CIT single photon emission computed tomography (SPECT) scanning of the nigrostriatal dopaminergic system. These results are a first step towards the development of a screening strategy that may be applied in the general population. Impairments of olfactory function, however, are not specific to PD but are also associated with other neurodegenerative disorders (e.g. Alzheimer's disease) and certain lifestyle characteristics (e.g. smoking). In the next few years our research efforts will focus on two different approaches to develop a more specific screening strategy. First, olfactory processing tasks will be combined with tasks aimed at detecting subtle (visuo)motor disturbances and early cognitive impairments. In parallel, an effort will be made to define disease-specific patterns of olfactory dysfunction in neurodegenerative disorders.

Aged↗

PubMed2001

Effects of dose, sex, and long-term abstention from use on toxic effects of MDMA (ecstasy) on brain serotonin neurons.

BACKGROUND: 3,4-methylenedioxymethamphetamine (MDMA or ecstasy) is a popular recreational drug that has been shown to damage brain serotonin neurons in high doses. However, effects of moderate MDMA use on serotonin neurons have not been studied, and sex differences and the long-term effects of MDMA use on serotonin neurons have not been identified. We investigated the effects of moderate and heavy MDMA use, sex differences, and long-term effects of MDMA use on serotonin neurons in different brain regions. METHODS: By means of flyers posted in "rave" venues in Amsterdam, the Netherlands, we recruited 15 moderate MDMA users, 23 heavy MDMA users, 16 ex-MDMA users who had stopped using MDMA for more than 1 year, and 15 controls who claimed never to have used MDMA. We studied the effects of MDMA on brain serotonin neurons using 123iodine-2beta-carbomethoxy-3beta-(4-iodophenyl) tropane ([123I]beta-CIT)-a radioligand that binds with high affinity to serotonin transporters. Density of binding (expressed as a ratio of region-of-interest binding over binding in the cerebellum) was calculated by single-photon-emission computed tomography (SPECT). FINDINGS: We saw significant effects of group and group by sex (p=0.041 and p=0.022, respectively) on overall [123I]beta-CIT binding ratios. In heavy MDMA users, significant decreases in overall binding ratios were seen in women (p<0.01) but not men (p=0.587). In female ex-MDMA users, overall densities of serotonin transporters were significantly higher than in heavy MDMA users (p=0.004), but not higher than in controls (p=0.524). INTERPRETATION: Our results indicate that heavy use of MDMA is associated with neurotoxic effects on serotonin neurons, that women might be more susceptible than men, and that MDMA-induced neurotoxic changes in several brain regions of female ex-MDMA users are reversible.

Adult↗

PubMed2001

Addition of a 5-HT receptor agonist to methylphenidate potentiates the reduction of [123I]FP-CIT binding to dopamine transporters in rat frontal cortex and hippocampus.

The neurotoxic potential of amphetamine and related drugs is well documented. However, methylphenidate, an amphetamine derivative used in the treatment of attention deficit hyperactivity disorder, and known to increase synaptic dopamine (DA) levels, seems to lack neurotoxic potential. It is hypothesized that both dopaminergic and serotonergic systems are involved in the neurotoxicity of amphetamine derivatives. The purpose of the present study was to evaluate the neurotoxic potential of methylphenidate and to test whether stimulation of the serotonergic system may confer neurotoxic properties to methylphenidate for DA or serotonin (5-HT) neurons. In addition, the present study was undertaken to evaluate the necessity to perform future SPECT studies in individuals using both methylphenidate and 5-HT-acting agents. We therefore measured monoaminergic transporters in rat brain using radioligands suitable for SPECT imaging ([123I]beta-CIT and [123I]FP-CIT). Groups of rats were treated with methylphenidate or saline for 4 days. Additional groups were treated with the selective 5-HT(2) receptor agonist quipazine or the selective 5-HT reuptake blocker fluoxetine, alone or in combination with methylphenidate. Binding studies were performed 5 days after the last treatment. In a second experiment, methylphenidate in combination with quipazine, along with a control group, was retested. In this experiment, monoaminergic terminal density was estimated 2 weeks (rather than 5 days) after drug treatment. Five days, but not 2 weeks, after treatment a significant reduction in specific [123I]FP-CIT binding was observed in the frontal cortex and hippocampus of rats treated with methylphenidate in combination with quipazine. These changes probably do not reflect neurotoxic changes of frontal cortex and hippocampal DA terminal markers, but a compensatory downregulation of DA transporters. These findings suggest potential harmful effects of concomitant use of drugs directly activating 5-HT2 receptors in patients using methylphenidate.

Animals↗

PubMed2001

Clinical and pathologic abnormalities in a family with parkinsonism and parkin gene mutations.

A Dutch family with autosomal recessive early-onset parkinsonism showed a heterozygous missense mutation in combination with a heterozygous exon deletion in the parkin gene. Although the main clinical syndrome consisted of parkinsonism, the proband clinically had additional mild gait ataxia and pathologically showed neuronal loss in parts of the spinocerebellar system, in addition to selective loss of dopaminergic neurons in the substantia nigra pars compacta. Lewy bodies and neurofibrillary tangles were absent, but tau pathology was found.

Aged↗

PubMed2001

Dopamine transporter density in young patients with schizophrenia assessed with [123]FP-CIT SPECT.

Disturbances in the dopamine (DA) system are thought to play a major role in schizophrenia. Amphetamine-induced release of endogenous DA is shown to be enhanced in schizophrenia, as is striatal [18F]FDOPA uptake in the striatum. It is not clear if the density of DA neurons is altered in schizophrenia. By studying the DA transporter with [123I]FP-CIT single photon emission computed tomography (SPECT), the density of nigrostriatal dopaminergic cells can be studied. Using [123I]FP-CIT SPECT, DA transporter density in the striatum was studied in 36 young patients with schizophrenia. Ten patients were antipsychotic (AP)-naive, 15 were treated with olanzapine, eight with risperidone and three were AP-free. A control group of 10 age-matched volunteers was included. Striatal [123I]FP-CIT binding was not significantly different between AP-naive patients (2.87), patients treated with olanzapine (2.76), patients treated with risperidone (2.76), AP-free patients (2.68) and controls (2.82) (F=0.07,p=0.98). Unexpectedly, striatal [123I]FP-CIT binding in females was significantly higher than in males (3.29 and 2.70, respectively; t=-2.56, p=0.014).Concluding, functional changes in the dopaminergic system in schizophrenia are not likely to be reflected in a change in DA transporter density. Moreover, DA transporter density does not seem to be altered by AP medication.

Adult↗

PubMed2001

Cortical serotonin transporter density and verbal memory in individuals who stopped using 3,4-methylenedioxymethamphetamine (MDMA or "ecstasy"): preliminary findings.

BACKGROUND: Although the popular drug 3,4-methylenedioxymethamphetamine (MDMA or "ecstasy") has been shown to damage brain serotonin (5-HT) neurons in animals, the fate and functional consequences of 5-HT neurons after MDMA injury are not known in humans. We investigated the long-term effects of MDMA use on cortical 5-HT neurons in humans and memory function, because brain 5-HT has been implicated in memory function. METHODS: Twenty-two recent MDMA users, 16 ex-MDMA users who had stopped using MDMA for more than 1 year, and 13 control subjects. The effects of MDMA use on cortical 5-HT neurons was studied by means of single-photon emission computed tomography with iodine 123-labeled 2beta-carbomethoxy-3beta-(4-iodophenyl) tropane ([(123)I]beta-CIT) by quantification of brain 5-HT transporter densities. Verbal memory performance was assessed with the Rey Auditory Verbal Learning Test. RESULTS: Mean cortical [(123)I]beta-CIT-labeled 5-HT transporter density was significantly lower in recent MDMA users than in controls (1.17 vs. 1.28 [-9%]) but not in ex-MDMA users (1.24 vs. 1.28 [-3%]). Recent and ex-MDMA users recalled significantly fewer words than did controls on the immediate recall (47.0 and 48.0 vs 60.0, respectively; P =.001) as well as the delayed recall (9.8 and 10.1 vs. 13.1, respectively; P =.003). Greater use of MDMA was associated with greater impairment in immediate verbal memory. However, memory performance was not associated with [(123)I]beta-CIT binding to cortical 5-HT transporters or duration of abstinence from MDMA. CONCLUSION: The present study suggests that, while the neurotoxic effects of MDMA on 5-HT neurons in the human cortex may be reversible, the effects of MDMA on memory function may be long-lasting.

Adult↗

PubMed2001

Imaging of dopamine transporters with [123I]FP-CIT SPECT does not suggest a significant effect of age on the symptomatic threshold of disease in Parkinson's disease.

Parkinson's disease (PD) is characterized neuropathologically by degeneration of the nigrostriatal dopaminergic pathway. With natural aging there is loss of dopaminergic cells in the substantia nigra and, consequently, loss of dopamine transporters in the striatum. It has been suggested that PD is caused by an accelerated rate of cell death. Conceptually, symptoms in idiopathic PD become apparent after a critical level of cell loss, the "symptom threshold." It has been suggested that this symptom threshold is independent of age. In this study, [123I]FP-CIT SPECT was used to assess the effect of aging on the density of striatal dopamine transporters in vivo in controls (n = 36) and early, drug-naive, patients with PD (n = 32). We found a significant age-associated decline of [123I]FP-CIT binding to striatal dopamine transporters in controls, but not in parkinsonian patients. This finding might give further support for the existence of an age-independent threshold in PD. In a subgroup of patients with hemi-PD, we found a significant loss of dopamine transporters bilaterally in the caudate nucleus and putamen. This loss was more pronounced in the putamen than in the caudate nucleus and the contralateral binding was significantly lower than the ipsilateral binding. By using age-corrected data, we estimated that in our particular patient group motor signs started when the loss of [123I]FP-CIT binding ratios in the putamen was 46-64%.

Adult↗

PubMed2001

Subclinical dopaminergic dysfunction in asymptomatic Parkinson's disease patients' relatives with a decreased sense of smell.

By the time a clinical diagnosis of Parkinson's disease (PD) is made, a significant loss of dopaminergic neurons has already occurred. Identifying patients in the period between the presumed onset of dopaminergic cell loss and the appearance of clinical parkinsonism may be of major importance in the development of effective neuroprotective treatment strategies. In an effort to develop a feasible strategy to detect preclinical PD, a combination of olfactory processing tasks, including odor detection, odor identification, and odor discrimination was used to select groups of hyposmic and normosmic individuals from a total of 250 relatives (parents, siblings, or children) of subjects with PD. Single photon emission computed tomography (SPECT) with [123I]beta-CIT as a dopamine transporter ligand was used to assess nigrostriatal dopaminergic function in 25 hyposmic and 23 normosmic relatives of PD patients. An abnormal reduction in striatal dopamine transporter binding was found in 4 out of 25 hyposmic relatives of PD patients, two of whom subsequently developed clinical parkinsonism, and in none of the 23 normosmic relatives. These observations demonstrate that subclinical reductions in dopamine transporter binding can be detected in asymptomatic relatives of sporadic PD patients by means of [123I]beta-CIT and SPECT. The results further indicate that olfactory deficits may precede clinical motor signs in PD.

Aged↗

PubMed2001

Rigidity decreases resting tremor intensity in Parkinson's disease: A [(123)I]beta-CIT SPECT study in early, nonmedicated patients.

Tremor is one of the clinical hallmarks of Parkinson's disease (PD). Although it is accepted that other classic symptoms of PD such as rigidity and bradykinesia result from a degeneration of the nigrostriatal system and subsequent reduction in striatal dopamine, the pathophysiology of resting tremor remains unclear. The majority of recent single photon emission computed tomography (SPECT) and positron emission tomography (PET) studies, using various radioligands, demonstrated significant correlation between striatal radioligand bindings and the degree of parkinsonian symptoms such as rigidity and bradykinesia, but not tremor. We investigate the relationship between the degeneration of the nigrostriatal pathway and the appearance of resting tremor, taking into account the possible interference of rigidity with the resting tremor. Thirty early and drug-naïve PD patients were examined. Tremor and rigidity of the arms were assessed using UPDRS, and the power of tremor was estimated using spectral analysis of tremor peaks. [(123)I]beta-CIT SPECT was used to assess degeneration of the dopaminergic system in PD patients. A comparison between asymmetry indices showed that in terms of both tremor and rigidity, the most affected arm corresponded significantly with the contralateral striatum, having the largest reduction in radioligand binding. Furthermore, tremor power accounted for a significant part of variance in the contralateral striatum, suggesting a relationship between this PD symptom and the degeneration of the dopaminergic system. Further, the degree of tremor was reduced with increasing rigidity. However, correcting for the influence of rigidity, the significant contribution of tremor in the variance in the contralateral striatal [(123)I]beta-CIT binding disappeared. When the confounding influence of rigidity is taken into account, no significant direct relationship between dopaminergic degeneration and the degree of tremor could be found. Other pathophysiological mechanisms should be similarly investigated in order to further our understanding of the origin of resting tremor in PD.

Adult↗

PubMed2001

Dopamine transporter density in patients with tardive dyskinesia: a single photon emission computed tomography study.

RATIONALE: Tardive dyskinesia occurs frequently in schizophrenic patients chronically treated with classical antipsychotic medication. It may be caused by loss of dopaminergic cells, due to free radicals as a product of high synaptic dopamine levels. OBJECTIVE: To evaluate dopamine transporter density in the striatum in patients with tardive dyskinesia. METHODS: Striatal [123I]FP-CIT binding was measured with SPECT in seven schizophrenic patients with tardive dyskinesia and eight healthy controls. RESULTS: No significant difference was found between striatal [123I]FP-CIT binding ratios in patients with tardive dyskinesia and controls. CONCLUSIONS: This preliminary study indicates no change in striatal dopamine transporter density in schizophrenic patients with tardive dyskinesia. This finding does not support the hypothesis that tardive dyskinesia is caused by dopaminergic cell loss.

Adult↗

PubMed2001

Higher occupancy of muscarinic receptors by olanzapine than risperidone in patients with schizophrenia. A[123I]-IDEX SPECT study.

RATIONALE: In vitro data have shown anticholinergic properties of the atypical antipsychotic drug olanzapine. Substantial occupancy of muscarinic receptors may be an explanation for the low incidence of extrapyramidal side effects induced by olanzapine. OBJECTIVES: To obtain an in vivo measurement of muscarinic receptor occupancy by olanzapine compared with risperidone in patients with schizophrenia stabilised on medication. METHODS: Five patients with schizophrenia treated with olanzapine and five patients treated with risperidone were studied. Muscarinic receptor occupancy in the striatum and cortex was studied in vivo with SPECT using [123I]-IDEX as a radioligand. SPECT data were compared with those of six healthy subjects. RESULTS: Patients stabilised on olanzapine showed significantly lower mean (+/-SD) striatal and cortical (1.50+/-0.21 and 1.51+/-0.22, respectively) muscarinic receptor binding ratios of [123I]-IDEX (reflecting higher levels of muscarinic receptor occupancy) than controls (3.91+/-0.61 and 3.65+/-0.70, respectively). Furthermore, [123I]-IDEX binding ratios in patients treated with risperidone were slightly lower than controls, reaching significance only in the striatum (2.99+/-0.27 versus 3.91+/-0.61, for risperidone and controls). CONCLUSIONS: The substantial occupancy of muscarinic receptors in the striatum and cortex by olanzapine may be an explanation for the low incidence and severity of extrapyramidal side effects of this antipsychotic drug. Furthermore, it may also explain the anticholinergic side effects of olanzapine.

Adolescent↗

PubMed2001

The clinical benefit of imaging striatal dopamine transporters with [123I]FP-CIT SPET in differentiating patients with presynaptic parkinsonism from those with other forms of parkinsonism.

[123I]FP-CIT (N-omega-fluoropropyl-2 beta-carbomethoxy-3 beta-(4-iodophenyl)nortropane) has been developed successfully as a radioligand for single-photon emission tomography (SPET) imaging of dopamine transporters, which are situated in the membrane of dopaminergic neurons. Imaging of these transporters has shown promise as a clinical tool to detect degeneration of the dopaminergic nigrostriatal pathway. Several "presynaptic parkinsonian" syndromes, such as Parkinson's disease or multiple system atrophy, are characterised by degeneration of the nigrostriatal pathway. [123I]FP-CIT SPET imaging studies have shown the ability to detect loss of striatal dopamine transporters in such syndromes. However, in clinical practice it is sometimes difficult, but important, to discriminate patients with "presynaptic parkinsonism" from those with other forms of parkinsonism not characterised by loss of presynaptic dopaminergic cells (e.g. psychogenic parkinsonism or drug-induced postsynaptic parkinsonism). In these inconclusive cases, it may be of value to confirm or exclude the existence of degeneration of nigrostriatal dopaminergic cells by using imaging techniques such as [123I]FP-CIT SPET. Using [123I]FP-CIT SPET, we have imaged the striatal dopamine transporters in a group of patients with inconclusive forms of parkinsonism, and, moreover, have been able to perform clinical follow-up of these patients 2-4 years after imaging. In 33 inconclusive cases, ratios of specific to non-specific binding were calculated for the caudate nucleus and putamen following [123I]FP-CIT SPET imaging and compared with ratios obtained in healthy controls. In nine of the patients, degeneration of the nigrostriatal pathway was found scintigraphically and in all these cases, presynaptic parkinsonism was confirmed by clinical follow-up. In the other 24 subjects no degeneration was found scintigraphically. Forms of parkinsonism other than the presynaptic were confirmed at follow-up in 19 cases, and in three cases no conclusive diagnosis was established, but presynaptic parkinsonism was excluded clinically. A clinical diagnosis of presynaptic parkinsonism was established in two cases: one case of multiple system atrophy (in this patient loss of dopamine D2 receptors was found with [123I]iodobenzamide SPET performed 2 weeks after [123I]FP-CIT imaging) and one case of Parkinson's disease. Our data suggest that the positive predictive value of [123I]FP-CIT imaging is very high, and although the negative predictive value is lower, dopamine transporter imaging offers the prospect of a quick, objective method to confirm or exclude presynaptic parkinsonism in inconclusive cases.

Adolescent↗

PubMed2001

[123I]FP-CIT SPECT is a useful method to monitor the rate of dopaminergic degeneration in early-stage Parkinson's disease.

We investigated the applicability [123I]FP-CIT SPECT for the assessment of the rate of dopaminergic degeneration in PD. Twenty early-stage PD patients (age range 43-73 yr; mean age 55.4) were examined twice, a mean of 12 months apart. The mean annual change in the ratio of specific to nonspecific [123I]FP-CIT binding to the striatum was used as the outcome measure. The mean annual decrease in striatal [123I]FP-CIT binding ratios was found to be about 8% (of the baseline mean). In order to demonstrate a significant effect (p < 0.05) of putative neuroprotective agent with 0.80 power and 50% of predicted protection within 2 years, 36 patients are required in each group, when the effects are measured by means of changes in [123I]FP-CIT binding ratios in whole striatum. Our findings indicate that [123I]FP-CIT SPECT seems to be a useful tool to investigate the progression of dopaminergic degeneration in PD and may provide an objective method of measuring the effectiveness of neuroprotective therapies.

Adult↗

PubMed2001

Evaluation of high-resolution pinhole SPECT using a small rotating animal.

UNLABELLED: Ex vivo measurements in animals are used frequently in the field of nuclear medicine for the characterization of newly developed radioligands and for drug development. In vivo SPECT would replace these ex vivo measurements in a relatively large number of cases if one were able to adequately image small organs. The pinhole collimator has been used extensively to obtain greater detail in planar imaging. However, using a pinhole collimator for SPECT is difficult because it requires a heavy collimated detector to rotate around a small object with a constant radius of rotation. METHODS: We have developed a mechanism in which the gantry and collimator are fixed and the animal rotates. Hollow cylinders of different sizes were made to enable imaging of small animals of different sizes: mice, hamsters, and rats. The cylinder is mounted on a stepping motor-driven system and positioned exactly above the pinhole collimator of an ARC3000 camera with a 1-mm pinhole insert. The stepping motor is controlled by the Hermes acquisition/processing system. After imaging each projection, a signal is given to rotate the stepping motor with the desired number of angular degrees. Filtered backprojection, adapted to pinhole SPECT, was used for reconstruction. The system allows adjustments of the radius of rotation and along the axis of the cylinder to select the field of view. Calibration experiments were performed to ensure that the axis of rotation was exactly in the middle of the cylinder. Phantom experiments were performed to assess sensitivity, spatial resolution, and uniformity of the system and to test the system for distortion artifacts. In addition, a brain dopamine transporter rat study and a hamster myocardial study were performed to test the clinical feasibility of the entire system. RESULTS: In the line source experiment, the spatial resolution obtained in air was 1.3 mm full width at half maximum, with a radius of rotation of 33 mm. Furthermore, the system has good uniformity and is capable of detecting cold spots of 2-mm diameter. The animal studies showed that it was feasible to image receptors or transporters and organs with sufficient detail in a practical setup. CONCLUSION: A rotating cylinder mechanism for pinhole SPECT is feasible and shows the same characteristics as conventional pinhole SPECT with a rotating camera head, without distortion artifacts. This mechanism permits pinhole SPECT to replace many ex vivo animal experiments.

3-Iodobenzylguanidine↗

PubMed2000

Memory disturbances in "Ecstasy" users are correlated with an altered brain serotonin neurotransmission.

RATIONALE: Methylenedioxymethamphetamine (MDMA) is known to damage brain pre-synaptic serotonin (5-HT) neurons. Since loss of 5-HT neurons has been implicated in memory loss, it is important to establish whether MDMA use may produce changes in postsynaptic 5-HT receptors and memory function in humans. OBJECTIVES: To investigate whether MDMA use leads to compensative alterations in post-synaptic 5-HT2A receptors and whether there is a relation with memory disturbances. METHODS: Brain cortical 5-HT2A receptor densities were studied with [123I]-5-I-R91150 SPECT in five abstinent MDMA users and nine healthy controls. Memory performance was assessed using RAVLT. RESULTS: [123I]-5-I-R91150 binding ratios were significantly higher in the occipital cortex of MDMA users than in controls, indicating up-regulation. Mean cortical 5-HT2A receptor binding correlated positively with RAVLT-recall in MDMA users. CONCLUSION: Our preliminary results may indicate altered 5-HT neuronal function with correlated memory impairment in abstinent MDMA users.

Adult↗

PubMed2000

Effect of age and gender on dopamine transporter imaging with [123I]FP-CIT SPET in healthy volunteers.

Dopamine transporter imaging is a valuable tool to investigate the integrity of the dopaminergic neurons. To date, several reports have shown an age-associated decline in dopamine transporters in healthy volunteers. Although animal studies suggest an effect of gender on dopamine transporter density, this gender effect has not yet been confirmed in human studies. To study the influence of age and gender on dopamine transporter imaging in healthy volunteers, we performed single-photon emission tomography imaging with [123I]FP-CIT to quantify dopamine transporters. Forty-five healthy volunteers (23 males and 22 females) were included, ranging in age from 18 to 83 years. SPET imaging was performed 3 h after injection of +/-110 MBq [123I]FP-CIT. An operator-independent volume of interest analysis was used for quantification of [123I]FP-CIT binding in the striatum. The ratio of specific striatal to non-specific [123I]FP-CIT binding was found to decrease significantly with age. Moreover, we found a high variance in [123I]FP-CIT binding in young adults. Finally, females were found to have significantly higher [123I]FP-CIT binding ratios than males. This effect of gender on [123I]FP-CIT binding ratios was not related to age. The results of this study are consistent with findings from previous studies, which showed that dopamine transporter density declines with age. The intriguing finding of a higher dopamine transporter density in females than in males is in line with findings from animal studies.

Adult↗

PubMed2000

[123I]FP-CIT binding in rat brain after acute and sub-chronic administration of dopaminergic medication.

The recently developed radioligand [123I]FP-CIT is suitable for clinical single-photon emission tomography (SPET) imaging of the dopamine (DA) transporter in vivo. To date it has remained unclear whether dopaminergic medication influences the striatal [123I]FP-CIT binding. The purpose of this study was to investigate the influence of this medication on [123I]FP-CIT binding in the brain. We used an animal model in which we administered dopaminomimetics, antipsychotics and an antidepressant. In vivo [123I]FP-CIT binding to the DA and serotonin transporters was evaluated after subchronic and acute administration of the drugs. The administered medication induced small changes in striatal [123I]FP-CIT binding which were not statistically significant. As expected, the DA reuptake blocker GBR 12,909 induced a significant decrease in [123I]FP-CIT binding. [123I]FP-CIT binding in the serotonin-rich hypothalamus was decreased only after acute administration of fluvoxamine. The results of this study suggest that dopaminergic medication will not affect the results of DA transporter SPET imaging with [123I]FP-CIT.

Animals↗

PubMed2000

Subjective experience and striatal dopamine D(2) receptor occupancy in patients with schizophrenia stabilized by olanzapine or risperidone.

OBJECTIVE: The authors' goal was to study the relationship between subjective experience during treatment with olanzapine or risperidone and dopamine D(2) receptor occupancy in stabilized patients with schizophrenia. METHOD: Subjective experience, psychopathology, and extrapyramidal symptoms were assessed, and D(2) receptor occupancy was determined with [(123)I]iodobenzamide single photon emission computed tomography, in 22 patients whose schizophrenia was stabilized by olanzapine or risperidone. RESULTS: Subjective experience, depression, and negative symptoms were related to dopamine D(2) receptor occupancy, but extrapyramidal symptoms were not. CONCLUSIONS: These results provide preliminary evidence that negative subjective experience is related to high D(2) receptor occupancy. Longitudinal study is required because this relationship may have implications for dosing strategies.

Adolescent↗