Biomedical subjects

Tetsuya Suhara

Publications and source records attributed to Tetsuya Suhara.

At least 19 recordsLinked to original sources

PubMed2007

In vivo mapping of substance P receptors in brains of laboratory animals by high-resolution imaging systems.

Neurotransmission mediated by substance P (SP) and NK(1) receptor has been implicated in the pathophysiology of analgesia, emesis and diverse neuropsychiatric conditions including depression and anxiety disorder. Several lines of clinical trials using NK(1) receptor antagonists have been conducted to date, and the efficiency of preclinical assessments for proof of concept and dose optimization could be greatly increased by configuring an in vivo analytical system that permits quantitative mapping of NK(1) receptors in the brains of small-size laboratory animals expressing "human-like" NK(1) receptors. Hence, we investigated the applicability of experimental animals, ranging from rodents to primates, to positron emission tomographic (PET) measurements with [(18)F]fluoroethyl-SPA-RQ, a modification of a recently established radioligand for NK(1) receptors. A pharmacokinetic assay could be performed for a rhesus monkey in an awake condition, which allows the circumvention of influences of anesthesia on SP neurotransmission. Coregistration of PET and magnetic resonance images acquired by small-animal-dedicated devices enabled detailed localization of NK(1) receptors in the gerbil and marmoset brains. The present study also revealed the potentials of SDZ NKT 343 as an antagonist for central NK(1) receptors. In conjunction with additional in vitro and ex vivo autoradiographic observations, our in vivo results have demonstrated a similarity in the binding pattern among the animals examined, justifying cross-species extrapolation of PET findings on the SP-NK(1) pathway.

Animals↗

PubMed2006

Memory and frontal lobe functions; possible relations with dopamine D2 receptors in the hippocampus.

Cerebral cortical regions are thought to be important for cognitive functions such as memory and executive function. Although the functional associations between dopamine D2 receptors and motor and cognitive functions have been extensively examined in the striatum using positron emission tomography (PET), the role of dopamine D2 receptors in extrastriatal regions has been unexplored. We aimed to investigate the relationship between dopamine D2 receptors in extrastriatal regions and the performance of a broad spectrum of cognitive functions including memory, language, attention, and executive function in healthy subjects. Extrastriatal dopamine D2 receptors were measured in 25 male subjects using PET with [(11)C]FLB457. After the PET scans, a battery of neuropsychological tests was administered to all subjects. We found that the binding potential (BP) of [(11)C]FLB457 in the hippocampus was positively correlated with memory function. Furthermore, BP of [(11)C]FLB457 in the hippocampus, but not in the prefrontal cortex, was associated with frontal lobe functions such as executive function and verbal fluency. Our findings suggest that dopamine D2 receptors in the hippocampus might affect the local hippocampal function, but also brain functions outside the hippocampus such as the prefrontal cortex.

Adult↗

PubMed2006

Changes in central 5-HT(1A) receptor binding in mesial temporal epilepsy measured by positron emission tomography with [(11)C]WAY100635.

OBJECTIVE: The possible involvement of the brain 5-HT(1A) receptor in epilepsy has been indicated in animal seizure models. Recent in vivo neuroimaging studies demonstrated decreased 5-HT(1A) receptor binding in epilepsy. Using positron emission tomography (PET) with [(11)C]WAY100635, we investigated 5-HT(1A) receptor binding in patients with mesial temporal lobe epilepsy and aimed to clarify the involvement of the brain 5-HT(1A) receptor system in epilepsy. METHOD: PET measurements with [(11)C]WAY100635 were performed on 23 healthy volunteers and 13 patients who were diagnosed with mesial temporal lobe epilepsy based on clinical symptoms and electroencephalogram (EEG) findings. They had non-lesional mesial temporal lobe epilepsy with unilateral EEG foci and no hippocampal atrophy on magnetic resonance imaging. The binding potential (BP) of [(11)C]WAY100635 was calculated by the reference tissue model method. Data were analyzed for each region of interest (ROI) and on a voxel-by-voxel basis by statistical parametric mapping (SPM) system. RESULTS: ROI and voxel-based analyses consistently demonstrated that 5-HT(1A) receptor BP was significantly decreased in the temporal lobe, hippocampus and amygdala on the ipsilateral side of the EEG focus compared to controls. In addition, decreased 5-HT(1A) receptor BP was also observed on the contralateral side of the amygdala. CONCLUSION: 5-HT(1A) receptor binding in patients with mesial temporal lobe epilepsy decreased predominantly in the ipsilateral mesial temporal lobe structures but also in the contralateral side. The imaging of 5-HT(1A) receptor binding by PET detects functional changes of the limbic system in mesial temporal lobe epilepsy, proving to be a sensitive and useful method.

Adult↗

PubMed2006

Role of ventral striatal dopamine D1 receptor in cigarette craving.

BACKGROUND: Several theories of cigarette craving suggest that dopaminergic function in the ventral striatum plays an important role. The objective of this study was to determine correlations between craving-related brain activation and dopamine D1 receptor (D1R) binding in smokers. METHODS: Twelve smokers and 12 nonsmoking controls underwent [(15)O]H(2)O-positron emission tomography activation study and D1R-binding study using [(11)C]SCH 23390, and the correlations between receptor binding and cue-induced regional cerebral blood flow (rCBF) changes were assessed. Consecutive D1R-binding changes were examined during a period of 6 months of postsmoking abstinence in five smokers. RESULTS: Cue-induced activation was observed in the left ventral striatum including the nucleus accumbens in smokers. D1R binding in the ventral striatum showed a negative relationship with cue-induced craving and rCBF changes. D1R binding was significantly low in smokers, and there was a trend of increase after smoking abstinence. CONCLUSIONS: D1R binding and cue-induced rCBF changes in the ventral striatum suggest the important role of D1R in this region in cigarette craving.

Adult↗

PubMed2006

Men and women show distinct brain activations during imagery of sexual and emotional infidelity.

Jealousy-related behaviors such as intimate partner violence and morbid jealousy are more common in males. Principal questionnaire studies suggest that men and women have different modules to process cues of sexual and emotional infidelity. We aimed to elucidate the neural response to sentences depicting sexual and emotional infidelity in men and women using functional magnetic resonance imaging. Although there was no sex difference in the self-rating score of jealousy for sexual and emotional infidelity, men and women showed different brain activation patterns in response to the two types of infidelity. During jealous conditions, men demonstrated greater activation than women in the brain regions involved in sexual/aggressive behaviors such as the amygdala and hypothalamus. In contrast, women demonstrated greater activation in the posterior superior temporal sulcus. Our fMRI results are in favor of the notion that men and women have different neuropsychological modules to process sexual and emotional infidelity. Our findings might contribute to a better understanding of the neural basis of the jealousy-related behaviors predominantly observed in males.

Adult↗

PubMed2006

Effects of repetitive transcranial magnetic stimulation on [11C]raclopride binding and cognitive function in patients with depression.

BACKGROUND: Several studies have demonstrated that repetitive transcranial magnetic stimulation (rTMS) elicits moderate antidepressant effects. Several previous studies suggested that the dopaminergic system might be related to this therapeutic action of rTMS. We attempted to determine the effects of chronic rTMS on central dopaminergic function in depression using positron emission tomography (PET) with [11C]raclopride. METHODS: Nine patients with depression were treated with 10 daily sessions of rTMS (10 Hz, 5 s train, 20 trains at 100% motor threshold per session) over the left dorsolateral prefrontal cortex (DLPFC). Each patient underwent two [11C]raclopride PET scans and neuropsychological tests - before rTMS and 1 day after rTMS. RESULTS: In five patients, the Hamilton Rating Scale for Depression (HRSD) significantly decreased. Patients showed significant improvement in verbal memory following rTMS. There were no changes in [11C]raclopride binding in the caudate nucleus and putamen after rTMS treatment. LIMITATIONS: Our sample size was limited, and our study was an open trial lacking sham-treated controls. CONCLUSION: This study suggests that rTMS may be effective for the treatment of depression and also may improve verbal memory function. We observed no changes in [11C]raclopride binding, suggesting that there was no measurable increase in the release of dopamine at the second PET scan. Several animal studies and healthy human studies have indicated that dopamine can be released soon after acute rTMS. Our results suggest that release of striatal dopamine induced by rTMS may be only transient, or that dopamine release may be attenuated following chronic rTMS.

Adult↗

PubMed2006

Regional cerebral blood flow changes associated with interoceptive awareness in the recovery process of anorexia nervosa.

BACKGROUND: An abnormality in regional cerebral blood flow (rCBF) in anorexia nervosa (AN) patients has been reported. There are very few studies that have investigated the rCBF changes in the recovery process of AN. METHODS: For eight female AN patients, we performed (123)I-IMP single photon emission computed tomography (SPECT) and four psychological assessments (Eating Disorder Inventory (EDI), Eating Attitude Test (EAT), Self-Rating Depression Scale (SDS) and State-Trait Anxiety Inventory (STAI)) both before and after inpatient-behavioral therapy. SPECT images were analyzed using statistical parametric mapping software. We also performed correlational analysis between rCBF and clinical variables. RESULTS: Following treatment, the patients showed significant body weight recovery. They showed significant improvement in EAT, SDS, STAI and a subscale of EDI - interoceptive awareness (IA) - but not in total EDI or other EDI subscales. Significant rCBF increases were observed in the precuneus, posterior cingulate cortex (PCC), right dorsolateral prefrontal cortex (DLPFC), anterior cingulate cortex (ACC) and medial prefrontal cortex (MPFC) by the treatment. Significant correlation was observed between rCBF of right DLPFC and IA score before treatment. CONCLUSIONS: Changes of rCBF in right DLPFC, ACC, MPFC, PCC and precuneus were related to the AN recovery process and might be associated with improvement of IA following treatment.

Adolescent↗

PubMed2006

The role of extrastriatal dopamine D2 receptors in schizophrenia.

Despite numerous studies on extrastriatal regions involved in schizophrenia, studies on the functional implications of dopamine (DA) D2 receptors in the extrastriatal regions, including the cortex and thalamus, are limited. We review postmortem and in vivo human imaging studies as well as animal studies, focusing on the function of extrastriatal DA D2 receptors and their role in the pathophysiology of schizophrenia. Based on recent findings, cortical DA D2 receptors may interact with the gamma-aminobutyric acid system to modulate DA transmission, and thalamic DA D2 receptors are likely to participate in sensory gating function into the prefrontal cortex. We have found decreased DA D2 receptors in the anterior cingulate cortex and thalamic subregions of patients with schizophrenia. These observations may suggest that alterations of extrastriatal DA D2 receptors are involved in dysregulation of DA transmission and sensory signals from the thalamus to the cortex. Excessive excitatory signals from the thalamus might flow into the cortical neurotransmission system, aggravating dysregulation of DA transmission in both the striatal and extrastriatal regions in schizophrenia. These notions suggest the need for future investigations of extrastriatal DA D2 receptor function to gain important clues regarding the pathogenesis and of possible treatments for schizophrenia.

Brain↗

PubMed2006

Quantitative analysis for estimating binding potential of the peripheral benzodiazepine receptor with [(11)C]DAA1106.

[(11)C]DAA1106 is a potent and selective ligand for the peripheral benzodiazepine receptor (PBR) with high affinity. It has been reported that the density of PBR is related to brain damage, so a reliable tracer method for the evaluation of PBR would be of use. We evaluated a quantification method of [(11)C]DAA1106 binding in simulated data and human brain data. In the simulation study, the reliability of parameters estimated from the nonlinear least-squares (NLS) method, graphical analysis (GA), and multilinear analysis (MA) was evaluated. In GA, variation of the estimated distribution volume (DV) was small. However, DV was underestimated as noise increased. In MA, bias was smaller, and variation of the estimated DV was larger than in GA. In NLS, although variation was larger than in GA, it was small enough in regions of interest analysis, and not only DV but also binding potential (BP), determined from the k(3)/k(4) without any constraint, could be estimated. The variation of BP estimated with NLS became larger as k(3) or k(4) became smaller. In human studies with normal volunteers, regions of interest were drawn on several brain regions, BP was calculated by NLS, and DV was also estimated by NLS, GA, and MA. As a result, DVs estimated with each method were well correlated. However, there was no correlation between BP with NLS and DV with NLS, GA, and MA, because of the variation of K(1)/k(2) between individuals. In conclusion, BP is estimated most reliably by NLS with the two-tissue compartment model.

Acetamides↗

PubMed2006

[2-11C]isopropyl-, [1-11C]ethyl-, and [11C]methyl-labeled phenoxyphenyl acetamide derivatives as positron emission tomography ligands for the peripheral benzodiazepine receptor: radiosynthesis, uptake, and in vivo binding in brain.

The peripheral benzodiazepine receptor (PBR) is widely expressed in peripheral tissues, blood cells, and in glia cells in the brain. We have previously developed two positron emission tomography (PET) ligands, N-(2-[(11)C],5-dimethoxybenzyl)-N-(5-fluoro-2-phenoxyphenyl)acetamide ([(11)C]2) and its [(18)F]fluoroethyl analogue ([(18)F]6), for the current investigation of PBR in the human brain. The aim of this study was to label the potent PBR agonist N-(4-chloro-2-phenoxyphenyl)-N-(isopropoxybenzyl)acetamide (3) and its ethyl (7) and methyl (8) homologues with (11)C and to evaluate them as PET ligands for PBR with mice, rats, and monkeys. Ligands [(11)C]3, [(11)C]7, and [(11)C]8 were synthesized by alkylation of phenol precursor 9 with 2-[2-(11)C]iodopropane ([(11)C]10), [1-(11)C]iodoethane ([(11)C]11), and [(11)C]iodomethane ([(11)C]12), respectively. The alkylating agent [(11)C]10 or [(11)C]11 was prepared by reacting CH(3)MgBr with [(11)C]CO(2), followed by reduction with LiAlH(4) and iodination with HI. In vitro quantitative autoradiography determined that 3, 7, and 8 had potent binding affinities (K(i) = 0.07-0.19 nM) for PBR in the rat brain. These [(11)C]ligands could pass across the blood-brain barrier and enter the rat brain (0.17-0.32% of injected dose per gram wet tissue). Ex vivo autoradiography showed that the [(11)C]ligands preferably distributed in the olfactory bulb and cerebellum, two regions with richer PBR density in the rat brain. The co-injection of PBR-selective 2 reduced the [(11)C]ligand binding in the two regions, suggesting that binding in the rat brain was specific to PBR. PET study determined that the [(11)C]ligands preferably accumulate in the occipital cortex of the monkey brain, a region with a high density of PBR in the primate brain. Moreover, in vivo binding of the methyl homologue [(11)C]8 in the monkey brain could be inhibited by PBR-selective 2 or 1, indicating that some of the [(11)C]8 binding was due to PBR. Metabolite analysis demonstrated that these [(11)C]ligands were metabolized by debenzylation to polar products mainly in the plasma.

Acetamides↗

PubMed2006

Age-related degeneration of corpus callosum measured with diffusion tensor imaging.

The corpus callosum is the major commissure connecting the cerebral hemispheres, and there is evidence of its change with aging. The sub-regions of the corpus callosum (genu, rostral body, anterior midbody, posterior midbody, isthmus, splenium) respectively comprise fibers connecting heteromodal- and unimodal-associated cortical regions, and it is known that abnormalities of the corpus callosum are correlated with abnormalities in cognition and behavior. Yet, little is known about changes in the tissue characteristics of its sub-regions. We assessed age-related changes in fractional anisotropy and mean diffusivity in the sub-regions of the corpus callosum using diffusion tensor imaging. We studied 42 healthy right-handed individuals aged 21-73 years. There were no significant interactions of sex x region. Age has significant negative correlation with fractional anisotropy in the genu (P < 0.001), rostral body (P < 0.001), and isthmus (P = 0.005). Fractional anisotropy of the anterior midbody was correlated negatively with age at a trend level (P = 0.022). Age was significantly positively correlated with mean diffusivity in the genu (P = 0.001), rostral body (P = 0.002), anterior midbody (P = 0.001), and isthmus (P = 0.001). Age-related changes were detected in the sub-regions where their projection areas are thought to be vulnerable to normal aging. This suggested that fractional anisotropy and mean diffusivity values of the corpus callosum sub-regions could serve as markers of disturbance across the respective projection areas.

Adult↗

PubMed2006

Age-related decline of dopamine synthesis in the living human brain measured by positron emission tomography with L-[beta-11C]DOPA.

Loss of dopamine synthesis in the striatum with normal human aging has been observed in the postmortem brain. To investigate whether there is age-associated change in dopamine synthesis in the extrastriatal brain regions similar to that in the striatum, positron emission tomography studies with (11)C-labelled l-DOPA were performed on 21 normal healthy male subjects (age range 20-67 years). Decline in the tissue fraction of gray matter per region of interest was also investigated. The overall uptake rate constant for each region of interest was quantified by the Patlak plot method using the occipital cortex as reference region. Regions of interest were set on the dorsolateral prefrontal cortex, lateral temporal cortex, medial temporal cortex, occipital cortex, parietal cortex, anterior cingulate, thalamus, midbrain, caudate nucleus, and putamen. Test-retest analysis indicated good reproducibility of the overall uptake rate constant. Significant age-related declines of dopamine synthesis were observed in the striatum and extrastriatal regions except midbrain. The decline in the overall uptake rate constant was more prominent than in the tissue fraction of gray matter. These results indicate that the previously demonstrated age-related decline in striatal dopamine synthesis extends to several extrastriatal regions in normal human brain.

Adult↗

PubMed2006

A dose-finding study of duloxetine based on serotonin transporter occupancy.

RATIONALE: Positron emission tomography (PET) has been utilized for determining the dosage of antipsychotic drugs. To evaluate the dosage of antidepressants such as selective serotonin reuptake inhibitors, serotonin transporter occupancy (5-HTT) is also a useful index. OBJECTIVES: We investigated the degree of 5-HTT occupancy with different doses of the antidepressant duloxetine and the time-course of 5-HTT occupancy using PET. METHODS: PET scans with [11C]DASB were performed before and after a single administration of duloxetine (5-60 mg), and three consecutive scans were performed after a single dose or repeated doses of 60 mg of duloxetine. RESULTS: 5-HTT occupancies by duloxetine were increased by 35.3 to 86.5% with dose and plasma concentration increments. The ED50 value of 5-HTT occupancy was 7.9 mg for dose and 3.7 ng/ml for plasma concentration. In the time-course of 5-HTT occupancy, mean occupancies were 81.8% at 6 h, 71.9% at 25 h, and 44.9% at 53 h after a single administration, and 84.3% at 6 h, 71.9% at 49 h, and 47.1% at 78 h after repeated administrations. CONCLUSIONS: Based on 5-HTT occupancy, 40 mg and more of duloxetine was needed to attain 80% occupancy, and 60 mg of duloxetine could maintain a high level of 5-HTT occupancy with a once-a-day administration schedule.

Adult↗

PubMed2006

Brain and whole body distribution of N-isopropyl-4-iodoamphetamine (I-123) in humans: comparison of radiopharmaceuticals marketed by different companies in Japan.

OBJECTIVE: Iodine-123 (123I)-labeled N-isopropyl-4-iodoamphetamine (IMP) has been used as a cerebral blood flow (CBF) tracer for single-photon emission computed tomography (SPECT). An autoradiographic (ARG) method has been developed for the quantitation of CBF by IMP and SPECT. Two IMPs (IMPA and IMPB) produced by different radiopharmaceutical companies are marketed in Japan. In the present study, whole-body distributions including brain and blood of the two IMPs were compared in the same human subjects. METHODS: Two brain SPECT studies using IMPA or IMPB were performed on separate days in six young healthy men. Whole-body scans were also obtained with a large field-of-view single-head gamma camera. One-point arterial blood sampling was performed at 10 min after injection of IMP to measure both the radioactivity concentrations of whole blood and of octanol-extracted components. RESULTS: No significant differences between the two tracers were observed in body distribution, tracer kinetics in brain, or regional distribution in brain. However, the octanol extraction fraction in blood was significantly different between the two tracers. Radiochemical purity was slightly but significantly different between the tracers. CONCLUSIONS: In the ARG method, arterial input function is determined by calibration of a standard input function with the radioactivity concentration of arterial whole blood. Because the standard input function in the ARG method was obtained using IMPA, the standard input function obtained for IMPB should be used when CBF is calculated by the ARG method with IMPB.

Adult↗

PubMed2006

Effects of image reconstruction algorithm on neurotransmission PET studies in humans: comparison between filtered backprojection and ordered subsets expectation maximization.

OBJECTIVES: Both reconstruction algorithms, filtered backprojection (FBP) and ordered subsets expectation maximization (OSEM), are widely used in clinical positron emission tomography (PET) studies. Image reconstruction for most neurotransmission PET scan data is performed by FBP, while image reconstruction for whole-body [18F]FDG scan data is usually performed by OSEM. Although several investigators have compared FBP and OSEM in terms of the quantification of regional radioactivity and physiological parameters calculated from PET data, only a few studies have compared the two reconstruction algorithms in PET studies that estimate neurotransmission, i.e., neuroreceptor and neurotransporter binding. In this study we compared mean regional radioactivity concentration in the late phase and binding potential (BP) between FBP and OSEM algorithms in neurotransmission PET studies for [11C]raclopride and [11C]DASB. METHODS: Dynamic PET scans with [11C]raclopride in 3-dimensional mode were performed on seven healthy subjects. Dynamic PET scans with [11C]DASB in 2-dimensional mode were performed on another seven subjects. OSEM images were post-filtered so that its transverse spatial resolution became similar to that of FBP with the same Hanning filter (Kernel FWHM 6 mm). In both PET studies we calculated the BP of [11C]raclopride and [11C]DASB by a reference tissue model for each ROI (region of interest). RESULTS: There was no significant difference in mean regional radioactivity concentration between FBP and OSEM for [11C]raclopride and [11C]DASB. Only +2.4 - +3.2%, but still a significant difference in BP of [11C]raclopride between FBP and OSEM was observed in the striatum. There was no significant difference in BP between FBP and OSEM in other than the striatum for [11C]raclopride and in all regions for [11C]DASB. In addition, there was no significant difference in root mean square error between FBP and OSEM when BP was calculated. CONCLUSIONS: The BP values were similar between FBP and OSEM algorithms with [11C]raclopride and [11C]DASB. This study indicates that OSEM can be used for human neurotransmission PET studies for calculating BP although OSEM was not necessarily superior to FBP in the present study.

Adult↗

PubMed2006

Time course of in vivo 5-HTT transporter occupancy by fluvoxamine.

The pharmacokinetics of drugs with specific binding sites in the brain needs to be evaluated at these sites. In this study, we measured the time course of the selective serotonin reuptake inhibitor fluvoxamine in the human brain based on serotonin transporter (5-HTT) occupancy by positron emission tomography. Consecutive positron emission tomography scans were performed using [11C]3-amino-4-(2-dimethylaminomethyl-phenylsulfanyl)-benzonitrile before, 5 hours, 26 hours, and 53 hours after 50 mg of fluvoxamine administration in 6 healthy male volunteers (mean, 24.3 +/- 4.8 years). Quantification was performed using the multilinear reference tissue model 2. Mean 5-HTT occupancies were 72.9% +/- 4.9% at 5 hours, 50.3% +/- 11.0% at 26 hours, and 24.7% +/- 15.3% at 53 hours, and plasma concentrations were 13.9 +/- 5.5 ng/mL at 5 hours, 5.1 +/- 3.2 ng/mL at 26 hours, and 1.5 +/- 1.7 ng/mL at 53 hours. The relationship between the plasma concentration of fluvoxamine and 5-HTT occupancy at these different time points was fitted to the law of mass action.

Adult↗

PubMed2006

Quantitative analysis of dopamine synthesis in human brain using positron emission tomography with L-[beta-11C]DOPA.

BACKGROUND AND OBJECTIVES: To estimate the presynaptic function of the central dopaminergic system, the rate of endogenous dopamine synthesis has been measured by using L-[beta-C]DOPA or 6-[F]fluoro-L-DOPA with positron emission tomography. However, the regional kinetics of L-[beta-C]DOPA in human brain have not been investigated in detail. In the present study, the regional kinetics of L-[beta-C]DOPA in normal human brain and the accuracy of the method for quantifying L-[beta-C]DOPA kinetics, employing reference regions, were investigated. METHODS: After intravenous injection of L-[beta-C]DOPA, dynamic scanning was performed on ten healthy subjects for 89 min. The overall uptake rate constant K was calculated by the kinetic and graphical approaches, in which the occipital cortex was used as a reference brain region. RESULTS: Regional distribution of K was similar to those of dopamine D2 receptor. A significant negative correlation was observed between the neutral amino acid concentration in plasma and the influx rate constant through the blood-brain barrier (K1). The K values calculated by graphical approach were in good agreement with the values calculated by kinetic approach for both experimental and simulated data. CONCLUSIONS: The regional distribution of K corresponds to that of the nigrostriatal and mesolimbic dopaminergic system. Negative correlation between neutral amino acid concentration and K1 supports the suggestion that L-DOPA is transported in a competitive fashion via the same carrier system as neutral amino acids at the blood-brain barrier. Because the graphical approach can obviate the need for an arterial input function, it is useful for investigating the rate of regional dopamine synthesis in neuropsychiatric and neurodegenerative diseases.

Adult↗

PubMed2006

Different effects of chronic phencyclidine on brain-derived neurotrophic factor in neonatal and adult rat brains.

The N-methyl-D-aspartate (NMDA) receptor and brain-derived neurotrophic factor (BDNF) are both known to play major roles in the normal development of the brain. We have hypothesized that the chronic blockade of NMDA with phencyclidine (PCP) may have a different effect on BDNF synthesis at different stages of development. In an acute experiment, rat pups and adult rats were injected with PCP (2.5, 5 or 10 mg/kg) at postnatal day (PD) 15 or 49, respectively. In a chronic experiment, rat pups were injected daily from PD 5 to PD 14 with PCP (2.5, 5 or 10 mg/kg), while adult rats were injected daily with the same dose from PD 39 to PD 48. BDNF levels in the hippocampus, striatum and frontal cortex were determined by ELISA assay 24 hours after the last injection. Chronic PCP treatment of neonatal rats induced a dose-dependent decrease in BDNF in the hippocampus but not in the frontal cortex and striatum. Single injection of PCP to rat pups showed a slight reduction of BDNF in the hippocampus but only at higher doses. In contrast to neonatal brain, neither acute nor chronic injection of PCP influenced BDNF in adult brain. These findings suggest that chronic blockade of NMDA receptor in the early neonatal period has an inhibitory effect on BDNF synthesis in the hippocampus and may impair normal neurodevelopment in rat pups.

Age Factors↗