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Kazuhiko Yanai

Publications and source records attributed to Kazuhiko Yanai.

At least 19 recordsLinked to original sources
PubMed2007

In vivo evaluation of P-glycoprotein modulation of 8 PET radioligands used clinically.

UNLABELLED: P-glycoprotein (P-gp) regulates the ability of endogenous and exogenous compounds to cross the blood-brain barrier. We investigated whether PET tracers used clinically for studying brain function are affected by P-gp. METHODS: Modulation of 8 radioligands by P-gp was assayed in mice by evaluating the effect of treatment with cyclosporine A (CsA) on uptake into the brain (assay 1) and the effect of treatment with a cold ligand of the corresponding radioligand on uptake of (11)C-verapamil, a representative radioligand for P-gp (assay 2). Brain-to-blood ratios were also examined as the other index to correct the delivery of radioligands. The radioligands investigated were (11)C-TMSX (adenosine A(2A) receptor), (11)C-MPDX (adenosine A(1) receptor), (11)C-PK11195 (peripheral benzodiazepine receptor), (11)C-flumazenil (central benzodiazepine receptor), (11)C-raclopride (dopamine D(2)-like receptor), (11)C-pyrilamine (histamine H(1) receptor), (11)C-PIB (amyloid plaque), and (11)C-donepezil (acetylcholine esterase). RESULTS: In assay 1, CsA treatment increased both the uptake and the brain-to-blood ratio of (11)C-TMSX, (11)C-MPDX, (11)C-flumazenil, and (11)C-donepezil among the 8 radioligands. In assay 2, in which 4 cold ligands were examined, cold verapamil slightly increased the brain-to-blood ratio of (11)C-verapamil, but TMSX, MPDX, and MPPF did not increase either parameter. CONCLUSION: Assay 1 was suitable for evaluating the P-gp modulation of radioligands. Among the 8 radioligands investigated, (11)C-TMSX, (11)C-MPDX, (11)C-flumazenil, and (11)C-donepezil were modulated by P-gp.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2006

Selective cognitive dysfunction in mice lacking histamine H1 and H2 receptors.

Previous pharmacological experiments provide conflicting findings that describe both facilitatory and inhibitory effects of neuronal histamine on learning and memory. Here, we examined learning and memory and synaptic plasticity in mice with a null mutation of gene coding histamine H1 or H2 receptor in order to clarify the role of these receptors in learning and memory processes. Learning and memory were evaluated by several behavioral tasks including object recognition, Barnes maze and fear conditioning. These behavioral tasks are highly dependent on the function of prefrontal cortex, hippocampus or amygdala. Object recognition and Barnes maze performance were significantly impaired in both H1 receptor gene knockout (H1KO) and H2 receptor gene knockout (H2KO) mice when compared to the respective wild-type (WT) mice. Conversely, both H1KO and H2KO mice showed better auditory and contextual freezing acquisition than their respective WT mice. Furthermore, we also examined long-term potentiation (LTP) in the CA1 area of hippocampus in H1KO and H2KO mice and their respective WT mice. LTP in the CA1 area of hippocampus was significantly reduced in both H1KO and H2KO mice when compared with their respective WT mice. In conclusion, our results demonstrate that both H1 and H2 receptors are involved in learning and memory processes for which the frontal cortex, amygdala and hippocampus interact.

Analysis of Variance↗
PubMed2006

Psychosis pathways converge via D2high dopamine receptors.

The objective of this review is to identify a target or biomarker of altered neurochemical sensitivity that is common to the many animal models of human psychoses associated with street drugs, brain injury, steroid use, birth injury, and gene alterations. Psychosis in humans can be caused by amphetamine, phencyclidine, steroids, ethanol, and brain lesions such as hippocampal, cortical, and entorhinal lesions. Strikingly, all of these drugs and lesions in rats lead to dopamine supersensitivity and increase the high-affinity states of dopamine D2 receptors, or D2High, by 200-400% in striata. Similar supersensitivity and D2High elevations occur in rats born by Caesarian section and in rats treated with corticosterone or antipsychotics such as reserpine, risperidone, haloperidol, olanzapine, quetiapine, and clozapine, with the latter two inducing elevated D2High states less than that caused by haloperidol or olanzapine. Mice born with gene knockouts of some possible schizophrenia susceptibility genes are dopamine supersensitive, and their striata reveal markedly elevated D2High states; suchgenes include dopamine-beta-hydroxylase, dopamine D4 receptors, G protein receptor kinase 6, tyrosine hydroxylase, catechol-O-methyltransferase, the trace amine-1 receptor, regulator of G protein signaling RGS9, and the RIIbeta form of cAMP-dependent protein kinase (PKA). Striata from mice that are not dopamine supersensitive did not reveal elevated D2High states; these include mice with knockouts of adenosine A2A receptors, glycogen synthase kinase GSK3beta, metabotropic glutamate receptor 5, dopamine D1 or D3 receptors, histamine H1, H2, or H3 receptors, and rats treated with ketanserin or aD1 antagonist. The evidence suggests that there are multiple pathways that convergetoelevate the D2High state in brain regions and that this elevation may elicit psychosis. This proposition is supported by the dopamine supersensitivity that is a common feature of schizophrenia and that also occurs in many types of genetically altered, drug-altered, and lesion-altered animals. Dopamine supersensitivity, in turn, correlates with D2High states. The finding that all antipsychotics, traditional and recent ones, act on D2High dopamine receptors further supports the proposition.

Animals↗
PubMed2006

The physiological and pathophysiological roles of neuronal histamine: an insight from human positron emission tomography studies.

Histamine neurons are exclusively located in the posterior hypothalamus, and project their fibers to almost all regions of the human brain. Although a significant amount of research has been done to clarify the functions of the histaminergic neuron system in animals, a few studies have been reported on the roles of this system in the human brain. In past studies, we have been able to clarify some of the functions of histamine neurons using different methods, such as histamine-related gene knockout mice or human positron emission tomography (PET). The histaminergic neuron system is known to modulate wakefulness, the sleep-wake cycle, appetite control, learning, memory and emotion. Accordingly we have proposed that histamine neurons have a dual effect on the CNS, with both stimulatory and suppressive actions. As a stimulator, neuronal histamine is one of the most important systems that stimulate and maintain wakefulness. Brain histamine also functions as a suppressor in bioprotection against various noxious and unfavorable stimuli of convulsion, drug sensitization, denervation supersensitivity, ischemic lesions and stress susceptibility. This review summarizes our works on the functions of histamine neurons using human PET studies, including the development of radiolabeled tracers for histamine H1 receptors (H1R: (11)C-doxepin and (11)C-pyrilamine), PET measurements of H1R in depression, schizophrenia, and Alzheimer's disease (AD), and studies on the sedative effects of antihistamines using H(2)(15)O and H1R occupancy in the human brain. These molecular and functional PET studies in humans are useful for drug development in this millennium.

Aging↗
PubMed2006

Enhanced antinociceptive effects of morphine in histamine H2 receptor gene knockout mice.

We have previously shown that antinociceptive effects of morphine are enhanced in histamine H1 receptor gene knockout mice. In the present study, involvement of supraspinal histamine H2 receptor in antinociception by morphine was examined using histamine H2 receptor gene knockout (H2KO) mice and histamine H2 receptor antagonists. Antinociception was evaluated by assays for thermal (hot-plate, tail-flick and paw-withdrawal tests), mechanical (tail-pressure test) and chemical (formalin and capsaicin tests) stimuli. Thresholds for pain perception in H2KO mice were higher than wild-type mice. Antinociceptive effects of intracerebroventricularly administered morphine were enhanced in the H2KO mice compared to wild-type mice. Intracerebroventricular co-administration of morphine and cimetidine produced significant antinociceptive effects in the wild-type mice when compared to morphine or cimetidine alone. Furthermore, zolantidine, a selective and hydrophobic H2 receptor antagonist, enhanced the effects of morphine in all nociceptive assays examined. These results suggest that histamine exerts inhibitory effects on morphine-induced antinociception through H2 receptors at the supraspinal level. Our present and previous studies suggest that H1 and H2 receptors cooperatively function to modulate pain perception in the central nervous system.

Analysis of Variance↗
PubMed2006

Recent advances in molecular pharmacology of the histamine systems: roles of C-terminal tails of histamine receptors.

G-protein-coupled receptors (GPCR) represent a large and diverse superfamily of integral membrane proteins to which histamine receptors belong. Increasing numbers of proteins have been identified to interact with the C-termini of GPCRs. These interactions are implicated in targeting, trafficking, and fine-tuning of signaling of GPCRs. Although the C-terminus of the histamine H2 receptor has been suggested to play in agonist-induced internalization of the receptor, roles of the C-termini of the other three histamine receptors are not known. To date, there is no protein identified to interact with the C-termini of histamine receptors.

Endocytosis↗
PubMed2006

Brain histamine H receptor occupancy of orally administered antihistamines measured by positron emission tomography with (11)C-doxepin in a placebo-controlled crossover study design in healthy subjects: a comparison of olopatadine and ketotifen.

AIMS: The strength of sedation due to antihistamines can be evaluated by using positron emission tomography (PET). The purpose of the present study is to measure histamine H(1) receptor (H(1)R) occupancy due to olopatadine, a new second-generation antihistamine and to compare it with that of ketotifen. METHODS: Eight healthy males (mean age 23.5 years-old) were studied following single oral administration of olopatadine 5 mg or ketotifen 1 mg using PET with (11)C-doxepin in a placebo-controlled crossover study design. Binding potential ratio and H(1)R occupancy were calculated and were compared between olopatadine and ketotifen in the medial prefrontal (MPFC), dorsolateral prefrontal (DLPFC), anterior cingulate (ACC), insular (IC), temporal (TC), parietal (PC), occipital cortices (OC). Plasma drug concentration was measured, and correlation of AUC to H(1)R occupancy was examined. RESULTS: H(1)R occupancy after olopatadine treatment was significantly lower than that after ketotifen treatment in the all cortical regions (P < 0.001). Mean H(1)R occupancies for olopatadine and ketotifen were, respectively: MPFC, 16.7 vs. 77.7; DLPFC, 14.1 vs. 85.9; ACC, 14.7 vs. 76.1; IC, 12.8 vs. 69.7; TC, 12.5 vs. 66.5; PC, 13.9 vs. 65.8; and OC, 19.5 vs. 60.6. Overall cortical mean H(1)R occupancy of olopatadine and ketotifen were 15% and 72%, respectively. H(1)R occupancy of both drugs correlated well with their respective drug plasma concentrations (P < 0.001). CONCLUSION: It is suggested that 5 mg oral olopatadine, with its low H(1)R occupancy and thus minimal sedation, could safely be used an antiallergic treatment for various allergic disorders. Abbreviations histamine H(1) receptor (H(1)R), histamine H(1) receptor occupancy (H(1)RO), dopamine D(2) receptor (D(2)R), positron emission tomography (PET), blood-brain barrier (BBB), binding potential ratio (BPR), distribution volume (DV).

Administration, Oral↗
PubMed2006

Altered emotional behavioral responses in mice lacking brain-type fatty acid-binding protein gene.

Brain-type fatty acid-binding protein (B-FABP) belongs to a family of intracellular lipid-binding proteins. B-FABP exhibits a binding affinity to long-chain fatty acids (FAs) whose effects on brain functions including development, emotion, learning and memory have been proposed. B-FABP is localized in the ventricular germinal cells in embryonic brain and astrocytes in developing and mature brain of rodents. In the present study we generated the mouse harboring a null mutation in the B-FABP gene and studied its phenotype. B-FABP mutant mice exhibited the enhanced anxiety and increased fear memory as well as the decreased content of docosahexaenoic acid (DHA) in their brain during the neonatal period without detection of any histological changes in the brain. In the adult brain, B-FABP was localized more numerously to the astrocytes in the amygdala and septal area than to those in the hippocampal area. Analysis of FA content in the amygdala of adult brain revealed that arachidonic and palmitic acids increased significantly in the mutant mice compared with wild-type. Furthermore, the response of N-methyl-d-aspartate receptor-mediated current to DHA in isolated neurons from B-FABP mutant brain was significantly decreased compared with that of wild-type, while no significant differences were detected in behavioral responses related to the spatial learning/memory or in the hippocampal long-term potentiation. These data indicate that B-FABP is crucially involved in the fear memory and anxiety through its binding with FAs and/or its own direct effects on pertinent metabolism/signaling of FAs.

Animals↗
PubMed2005

Effects of histamine H(3) antagonists and donepezil on learning and mnemonic deficits induced by pentylenetetrazol kindling in weanling mice.

Childhood epilepsy is one of the main risk factors for a variety of problems involving cognition and behavior. Pentylenetetrazol (PTZ) kindling is currently an acceptable model for epilepsy research. The objectives of this study are to clarify the learning and mnemonic characteristics of PTZ kindling in developing mice, and to examine the effects of thioperamide and JNJ-5207852, two histamine H(3) receptor antagonists and donepezil, an acetylcholinesterase (AChE) inhibitor, on learning and memory deficits induced by PTZ kindling in the brains of developing mice. PTZ kindling led to learning and mnemonic deficits as assessed by social discrimination, acoustic fear conditioning, water maze and passive avoidance tests. Thioperamide and JNJ-5207852, ameliorated PTZ kindling-induced learning and mnemonic deficits in all tests except for the water maze test. In addition, the learning and mnemonic impairments induced by PTZ kindling were significantly improved by donepezil in all tests. These findings suggest that histamine and acetylcholine are involved in the different processes of learning and memory in the brain and that histamine H(3) receptor antagonists might be useful in the treatment of cognitive impairment in epilepsy.

Animals↗
PubMed2005

Quinoline and benzimidazole derivatives: candidate probes for in vivo imaging of tau pathology in Alzheimer's disease.

Neurofibrillary tangles (NFTs), neuropil threads, and neuritic elements of senile plaques predominantly comprise hyperphosphorylated tau protein and represent pathological characteristics of Alzheimer's disease (AD). These lesions occur before the presentation of clinical symptoms and correlate with the severity of dementia. In vivo detection of these lesions would thus prove useful for preclinical diagnosis of AD and for tracking disease progression. The present study introduces three novel compounds, 4-[2-(2-benzoimidazolyl)ethenyl]-N,N-diethylbenzenamine (BF-126), 2-[(4-methylamino)phenyl]quinoline (BF-158), and 2-(4-aminophenyl)quinoline (BF-170), as candidate probes for in vivo imaging of tau pathology in the AD brain. When solutions of these compounds are injected intravenously into normal mice, these agents exhibit excellent brain uptake and rapid clearance from normal brain tissue. These compounds display relatively lower binding affinity to beta-amyloid fibrils and higher binding affinity to tau fibrils, compared with previously reported probe BF-168. In neuropathological examination using AD brain sections, BF-126, BF-158, and BF-170 clearly visualize NFTs, neuropil threads, and paired helical filament-type neuritis. Autoradiography using 11C-labeled BF-158 further demonstrated labeling of NFTs in AD brain sections. These findings suggest the potential usefulness of quinoline and benzimidazole derivatives for in vivo imaging of tau pathology in AD.

Aged↗
PubMed2005

Blockage of histamine H1 receptor attenuates social isolation-induced disruption of prepulse inhibition: a study in H1 receptor gene knockout mice.

RATIONALE: Histaminergic neurotransmission has been implicated in the pathophysiology of stress-related psychiatric diseases. Although several atypical antipsychotics are potent H1 antagonists, the clinical significance of interaction between atypical antipsychotics and H1 receptors is still unknown. OBJECTIVE: In this study, we investigated the effects of H1 receptors blockage on social isolation-induced behavioral changes in H1 receptor gene knockout (H1KO) mice and their wild-type (WT) mice. METHODS: Both H1KO and their WT mice were subjected to 4-week social isolation rearing after weaning (21 postnatal days). After the 4-week isolation period, mice behavioral changes were evaluated using behavioral tests. RESULTS: Locomotor activity in home cages was significantly lower in isolation-reared WT mice than in socially reared WT mice. However, no change in locomotor activity was observed between socially and isolation-reared H1KO mice. Social isolation significantly impaired prepulse inhibition (PPI) of startle response in WT mice but not in H1KO mice. In addition, social isolation significantly impaired spatial learning and memory in WT mice but not in H1KO mice. Furthermore, H1KO mice treated with methamphetamine (METH) showed no enhancement in isolation-induced disruption of PPI. A neurochemical study revealed that isolation-reared WT mice had significantly lower dopamine (DA) levels and slightly increased DA turnover in the cortex than socially reared WT mice. Conversely, isolation-reared H1KO mice showed significantly higher DA contents as compared with socially reared H1KO mice. CONCLUSION: The results of our study indicate that blockage of H1 receptor-mediated neurotransmission attenuates social isolation-induced behavioral changes and that the therapeutic effects of atypical antipsychotics are mediated, at least in part, by interaction with H1 receptors in the brain.

Animals↗
PubMed2005

Intrathecally-administered histamine facilitates nociception through tachykinin NK1 and histamine H1 receptors: a study in histidine decarboxylase gene knockout mice.

Intrathecal injection of histamine elicited behavioral responses consisting of scratching, biting and licking in conscious mice. To study the participation of histamine in pain perception, histidine decarboxylase knockout mice were examined for pain threshold by means of three different kinds of noxious stimuli: thermal nociception (hot-plate, tail-flick, and paw-withdrawal), mechanical nociception (tail-pressure), and chemical nociception (formalin test and capsaicin test). Mutant mice lacking histidine decarboxylase showed significantly fewer nociceptive responses to the hot-plate, tail-flick, paw-withdrawal, tail-pressure, formalin and capsaicin tests. Sensitivity to noxious stimuli in the histidine decarboxylase knockout mice was significantly lower when compared to the wild-type mice. The intrathecally-administered histamine (400 pmol) significantly shortened the latency in the histidine decarboxylase knockout mice, but not in the wild-type mice in tail-flick tests. Pyrilamine, a histamine H(1) receptor antagonist, but not ranitidine, a histamine H(2) receptor antagonist, produced inhibition of the induced behavioral responses in the tail-flick test when co-administered with histamine. Sendide, a tachykinin NK(1) receptor antagonist, inhibited histamine-induced nociceptive behavior in the histidine decarboxylase knockout mice. In contrast, the treatment with D-(-)-2 amino-5-phosponovaleric acid (D-APV), an N-methyl-D-aspartate (NMDA) receptor antagonist, did not prevent the induction of the behavioral responses by histamine. These studies substantiate the evidence that nociceptive behavior induced by intrathecal injection of histamine is largely mediated through tachykinin NK(1) and histamine H(1) receptors in the spinal cord.

2-Amino-5-phosphonovalerate↗
PubMed2005

Enhanced antinociception by intracerebroventricularly administered orexin A in histamine H1 or H2 receptor gene knockout mice.

Orexins are neuropeptides that are mostly expressed in the posterior and lateral hypothalamus, and related to the central control of appetite, arousal, and antinociception. Orexin neurons projected to the tuberomammillary nucleus and orexins may release histamine from the histamine neurons in this nucleus. Histamine is known to cause hypernociception. The roles of histamine H1 and H2 receptors in the orexin A-induced antinociception, however, have not been clarified yet. Here we studied the effects of histamine H1 and H2 receptors on orexin A-produced antinociception using histamine receptor knockout mice in four assays of nociception; the hot-plate, the tail-flick, the tail-pressure and the capsaicin tests. Furthermore we studied effects of histamine H1 and H2 receptor antagonists on orexin A-produced antinociception in C57BL/6 mice. The antinociceptive effects of i.c.v. orexin A were greater in histamine H1 receptor or H2 receptor knockout mice than in the wild-type mice in all four assays of pain. Furthermore, treatment of C57BL/6 mice with a combination of i.c.v. orexin A and d-chlorpheniramine (a histamine H1 receptor antagonist) or cimetidine (a histamine H2 receptor antagonist) showed a greater antinociception than i.c.v. orexin A alone in all four assays. These findings suggest the possibility that orexin A may activate H1 and H2 receptors in the supraspinal levels through the release of histamine from neurons, which might attenuate the antinociceptive effects of orexin A. Thus, the blocking of the histamine H1 or H2 receptor may produce antinociception and enhance the orexin A-induced antinociception.

Animals↗
PubMed2005

Effects of activation of central nervous histamine receptors in cardiovascular regulation; studies in H(1) and H(2) receptor gene knockout mice.

To elucidate the central roles of histamine receptors in cardiovascular regulatory system, systolic, mean, and diastolic blood pressures (BPs) and heart rate (HR) were examined in conscious H(1) receptor gene knockout (H(1)KO) mice, H(2) receptor gene knockout (H(2)KO) mice, H(1) and H(2) receptor gene double knockout (DKO) mice, and their respective control mice by the tail-cuff system. Histamine, histamine-trifluoromethyl-toluidine derivative (HTMT, an H(1) agonist), dimaprit (an H(2) agonist), and immepip (an H(3) agonist) were intrathecally administered to these KO mice and control mice. Basal BPs and HR were not different among these three KO mice and their control or wild-type mice. Intrathecal administration of histamine significantly increased BPs and decreased HR in control mice. The increases in BPs were produced by histamine in H(1)KO and H(2)KO mice and by HTMT and dimaprit in C57BL mice. The pressor responses by HTMT and dimaprit in C57BL mice were greater than those by histamine in H(1)KO and H(2)KO mice, although the same decreases in HR were induced by histamine in C57BL and H(1)KO mice and by dimaprit in C57BL mice. The selective stimulation of H(3) receptors by immepip produced a consistent decrease in BPs in control mice. These results obtained with the exogenous selective agonists of three histamine receptors suggest that the pressor responses to histamine are mediated through the stimulation of both H(1) and H(2) receptors, whereas the atropine-sensitive decrease in heart rate is mainly due to H(2) receptors which activate the vagal output to the heart.

Animals↗
PubMed2005

Effects of fexofenadine and hydroxyzine on brake reaction time during car-driving with cellular phone use.

Antihistamines are a mainstay treatment for allergic rhinitis; however, many older agents cause adverse events, including sedation and central nervous system (CNS) impairment. Research has shown sedating effects of antihistamines on driving; currently, no known study has examined whether cellular phone usage while driving further compounds impairment in individuals administered antihistamines. The aim of this study was to examine this endpoint. In a randomized, double-blind, placebo-controlled, three-way crossover study, healthy volunteers received fexofenadine HCl 120 mg, hydroxyzine HCl 30 mg and placebo. Brake reaction time (BRT) was used to examine driving performance across four conditions: driving only; driving while completing simple calculations; complex calculations; and conversing on a cellular phone. Subjective sedation assessments were also conducted. Brake reaction time with and without cellular phone usage in fexofenadine-treated subjects did not differ significantly from placebo in any condition. In contrast, hydroxyzine-treated subjects were significantly more sedated and had slower BRTs, suggesting slower hazard recognition and brake application, compared with the fexofenadine and placebo groups in all conditions. Importantly, cellular phone operation was an additive factor, increasing BRTs in hydroxyzine-treated volunteers. Fexofenadine did not impair CNS function in subjects involved in a divided attention task of driving and cellular phone operation.

Adult↗
PubMed2005

Use of reference tissue models for quantification of histamine H1 receptors in human brain by using positron emission tomography and [11c]doxepin.

The aim of the present study is to evaluate the validity of the simplified reference tissue model (SRTM) and of Logan graphical analysis with reference tissue (LGAR) for quantification of histamine H1 receptors (H1Rs) by using positron emission tomography (PET) with [11C]doxepin. These model-based analytic methods (SRTM and LGAR) are compared to Logan graphical analysis (LGA) and to the one-tissue model (1TM), using complete datasets obtained from 5 healthy volunteers. Since HIR concentration in the cerebellum can be regarded as negligibly small, the cerebellum was selected as the reference tissue in the present study. The comparison of binding potential (BP) values estimated by LGAR and 1TM showed good agreement; on the other hand, SRTM turned out to be unstable concerning parameter estimation in several regions of the brain. By including the results of noise analysis, LGAR became a reliable method for parameter estimation of [11C]doxepin data in the cortical regions.

Adult↗
PubMed2005

Histamine H1 receptors in schizophrenic patients measured by positron emission tomography.

Increasing evidence has shown that the histaminergic neuron system is implicated in the pathophysiology of schizophrenia. The aim of this study was to compare the distribution of histamine H1 receptors between schizophrenics and normal human subjects in vivo using positron emission tomography (PET). H1 receptor binding was measured in 10 normal subjects and 10 medicated schizophrenic patients by PET and [11C] doxepin, a radioligand for the H1 receptor. The binding potential (BP=Bmax/K(D)) of [11C] doxepin for available brain H1 receptors was calculated by a graphical analysis on voxel-by-voxel basis and compared between schizophrenics and normal subjects using the regions of interest (ROIs) and the statistical parametrical mapping (SPM99). BP values for H1 receptors in the frontal and prefrontal cortices and the cingulate gyrus were significantly lower among the schizophrenic patients than among the control subjects. On the contrary, there were no areas of the brain where H1 receptors were significantly higher among the schizophrenic patients than the control subjects. The results of our study suggest that the central histaminergic neuron system could be involved in the pathophysiology of schizophrenia, although further studies are needed to confirm this hypothesis.

Adult↗