M2/M4 muscarinic receptor binding in the anterior cingulate cortex in schizophrenia and mood disorders

We have previously shown a decrease in [(3)H]pirenzepine binding to M1/M4 muscarinic receptors in the anterior cingulate cortex in schizophrenia but not in major depression or bipolar disorder. The present study aimed to extend these findings by examining the binding of [(3)H]AF-DX 384 to M2/M4 receptors in the same cohort of subjects. Using quantitative autoradiography we measured [(3)H]AF-DX 384 binding in the anterior cingulate cortex of 15 schizophrenia, 15 bipolar, 15 major depression and 15 control cases. Post-mortem tissue was obtained from the Stanley Foundation Brain Bank. [(3)H]AF-DX 384 binding had a homogenous distribution amongst the layers of the anterior cingulate cortex, was higher in males than in females and declined with prolonged storage of tissue. An inverse correlation between [(3)H]AF-DX384 binding and age of onset of the disease was observed in the schizophrenia group suggesting that the earlier the age at onset the higher the binding was. In the depression group, there was a significant effect of gender on [(3)H]AF-DX 384 binding with females having lower binding in comparison to males. In the bipolar group, there was a significant inverse correlation between antipsychotic medication and [(3)H]AF-DX 384 binding, suggesting that the higher the dose of medication the lower the binding was. No differences in [(3)H]AF-DX 384 binding were seen between the four groups. The present results provide no evidence of M2/M4 receptor alterations in the anterior cingulate cortex in schizophrenia and affective disorders and extend the body of evidence implicating cortical M1 but not M2 involvement in the pathology and pharmacotherapy of schizophrenia.     

Alterations of muscarinic and GABA receptor binding in the posterior cingulate cortex in schizophrenia

The posterior cingulate cortex (PCC), a key component of the limbic system, has been implicated in the pathology of schizophrenia because of its sensitivity to NMDA receptor antagonists. Recent studies have shown that the PCC is dysfunctional in schizophrenia, and it is now suspected to be critically involved in the pathogenesis of schizophrenia. Studies also suggest that there are abnormalities in muscarinic and GABAergic neurotransmission in schizophrenia. Therefore, in the present study we used quantitative autoradiography to investigate the binding of [(3)H]pirenzepine, [(3)H]AF-DX 384 and [(3)H]muscimol, which respectively label M1/4 and M2/4 muscarinic and GABA(A) receptors, in the PCC of schizophrenia and control subjects matched for age and post-mortem interval. The present study found that [(3)H]pirenzepine binding was significantly decreased in the superficial (-24%, p=0.002) and deep (-35%, p<0.001) layers of the PCC in the schizophrenia group as compared with the control group. In contrast, a dramatic increase in [(3)H]muscimol binding was observed in the superficial (+112%, p=0.001) and deep layers (+100%, p=0.017) of the PCC in the schizophrenia group. No difference was observed for [(3)H]AF-DX 384 binding between the schizophrenia and control groups. The authors found a significant inverse correlation between [(3)H]pirenzepine binding in the deep cortical layers and [(3)H]muscimol binding in the superficial layers (rho=-0.732, p=0.003). In addition, negative correlations were also found between age and [(3)H]pirenzepine binding in both superficial and deep cortical layers (rho=-0.669 p=0.049 and rho=-0.778, p=0.014), and between age of schizophrenia onset and [(3)H]AF-DX 384 binding (rho=-0.798, p=0.018). These results for the first time demonstrated the status of M1/M4, M2/M4 and GABA(A) receptors in the PCC in schizophrenia. Whilst the exact mechanism causing these alterations is not yet known, a possible increased acetylcholine and down regulated GABA stimulation in the PCC of schizophrenia is suggested.     

Muscarinic1 and 2 receptor mRNA in the human caudate-putamen: no change in m1 mRNA in schizophrenia

Studies using tissue obtained at autopsy suggest that changes in cholinergic neurons could be important in the pathology of schizophrenia.1-4 We have previously reported a decrease in [3H]pirenzepine binding5 and [3H]AF-DX 384 binding6 to caudate-putamen (CP) from subjects who had schizophrenia. Under the conditions chosen, [3H]pirenzepine would predominately bind to muscarinic1 (M1) and muscarinic4 (M4) receptors,7whereas [3H]AF-DX 384 would mainly bind to muscarinic2 (M2) and M4 receptors.8 Given the relative concentrations of M1, M2 and M4 receptors in the human CP and the magnitude of the decreases in radioligand binding in schizophrenia, our results most likely reflected a change in the density of M1 and M2 receptors in the CP from the schizophrenic subjects. In situ hybridisation has now been used to determine levels of m1 and m2 mRNA in CP from 14 schizophrenic and 16 control subjects previously used for radioligand binding. m2 mRNA in the CP from the schizophrenic and control subjects was below the sensitivity of in situhybridisation. There was no difference in the levels of m1 mRNA in CP from schizophrenic and control subjects (mean +/- SEM: 103 +/- 16 vs106 +/- 17 fmol [35S]oligonucleotide probe g-1estimated tissue equivalents, P = 0.91). In conclusion, data from our radioligand binding studies show decreases in [3H]pirenzepine binding that are likely to reflect a decrease in the density of M1 receptors in CP from schizophrenic subjects. Our data in this study show the absence of a concomitant change in mRNA coding for that receptor.     

Olanzapine treatment decreases the density of muscarinic M2 receptors in the dorsal vagal complex of rats

In this study, we investigated the effects of antipsychotic drugs, olanzapine and haloperidol, on the density of the muscarinic M2 receptors in the dorsal vagal complex (DVC) and hypoglossal nucleus (HN). Female Sprague Dawley rats were treated with olanzapine, haloperidol or vehicle (control) for 1 (short-term) or 12 weeks (long-term). Quantitative autoradiography was used to investigate the M2 receptor density in the DVC and HN using a muscarinic antagonist [(3)H] AF-DX384. Olanzapine, but not haloperidol, treatment induced a significant decrease in the binding density of M2 receptors in the DVC compared to control groups. Although the HN showed a higher density of [(3)H] AF-DX384 binding than the DVC, treatment with both olanzapine and haloperidol did not induce any significant changes in [(3)H] AF-DX384 binding in the HN. These results suggest that olanzapine-induced body weight gain may be associated with functional changes in the muscarinic neurotransmission in the DVC.     

Low muscarinic receptor binding in prefrontal cortex from subjects with schizophrenia: a study of Brodmann's areas 8, 9, 10, and 46 and the effects of neuroleptic drug treatment

OBJECTIVE: Aberrant cholinergic inputs and synaptic neurotransmission in the prefrontal cortex induce cognitive impairment, which is a central feature of schizophrenia. Postsynaptic excitatory muscarinic cholinergic M(1) and M(4) receptors are the major cholinoceptive targets in the prefrontal cortex and hence may be involved in the pathology and/or pharmacotherapeutics of schizophrenia. METHOD: Using quantitative autoradiography, the authors analyzed the binding of the M(1)/M(4) receptor selective antagonist [(3)H]pirenzepine in prefrontal cortex (Brodmann's areas 8, 9, 10, and 46) from schizophrenia patients who had (N=6) or had not (N=11) been treated with the anticholinergic agent benztropine mesylate and from normal comparison subjects (N=20). Moreover, preliminary studies of [(3)H]pirenzepine binding in rat frontal cortex following administration of antipsychotic drugs or benztropine mesylate were performed. RESULTS: Relative to those of comparison subjects, the mean levels of [(3)H]pirenzepine binding were significantly lower in Brodmann's areas 9 and 46 of the schizophrenia patients not treated with benztropine mesylate (18% lower in Brodmann's area 9 and 21% lower in Brodmann's area 46) and in all four examined regions of the patients who had received benztropine (51%-64% lower). Antipsychotic or anticholinergic drugs tended to increase or have no effect on the density of [(3)H]pirenzepine-labeled receptors in rat frontal cortex. CONCLUSIONS: Because M(1) and M(4) receptors are critical to the functions of prefrontal cortical acetylcholine, the present findings suggest a functional impairment in cholinergic neurotransmission in schizophrenia and the possibility that muscarinic receptors are involved in the pharmacotherapeutics of the disorder.     

Decreased muscarinic receptor binding in subjects with schizophrenia: a study of the human hippocampal formation.

BACKGROUND: Acetylcholine is important to hippocampal function, including the processes of learning and memory. Patients with schizophrenia show impaired learning and memory and hippocampal dysfunction. Thus, acetylcholinergic systems may be primarily or secondarily disrupted in the hippocampal formation of schizophrenic patients. The present study tested the hypothesis that [(3)H]pirenzepine-labeled muscarinic cholinergic receptor levels are altered in the hippocampal formation of patients with schizophrenia. METHODS: We have used quantitative autoradiography to measure [(3)H]pirenzepine binding to M(1) and M(4) receptors in the hippocampal formation from 15 schizophrenic and 18 nonschizophrenic subjects. RESULTS: The mean density of [(3)H]pirenzepine binding was reduced in all regions studied, including the dentate gyrus, subdivisions of Ammon's Horn (CA1-CA4), subiculum, and the parahippocampal gyrus, of the schizophrenic cohort. Moreover, unlike controls, there was no significant variation between the mean levels of [(3)H]pirenzepine binding across the subregions of the hippocampal formation from schizophrenic subjects. CONCLUSIONS: These findings provide support for a possible involvement of the muscarinic cholinergic system in the pathology and/or treatment of schizophrenia.     

Decreased density of serotonin 2A receptors in the superior temporal gyrus in schizophrenia-a postmortem study

The superior temporal gyrus (STG) is strongly implicated in the pathophysiology of schizophrenia, particularly with regards to auditory hallucinations. In this study, using in situ quantitative autoradiography in postmortem tissue, we investigated the binding of the [³H]ketanserin to 5-HT_2A receptors and [³H]mesulergine to 5-HT_2C receptors in the left STG of 8 male schizophrenic patients compared to 8 control subjects. A strong [³H]ketanserin binding was observed in the STG, however there was a very weak [³H]mesulergine binding in the STG. A significant decrease in binding of [³H]ketanserin was clearly observed in schizophrenia patients in comparison with control subjects. There were no significant correlations between 5-HT_2A binding density and age, postmortem intervals, or brain pH. These results suggest that the alterations of the 5-HT_2A receptors contribute to the pathophysiology of the STG in schizophrenia. Furthermore, there is a clear tendency for a positive correlation between 5-HT_2A and muscarinic M1 receptor bindings, and for negative correlations between 5-HT_2A and GABA_A receptor bindings and between muscarinic M1 and GABA_A receptor bindings. This provides a possible mechanism of auditory hallucinations through interactions between 5-HT_2A, acetylcholine muscarinic and GABA transmissions in the STG in schizophrenia.     

Increased diisopropylfluorophosphate-induced toxicity in mu-opioid receptor knockout mice

The potential involvement of mu-opioid receptors in mediating the changes of toxic signs and muscarinic receptor bindings after acute administration of irreversible antiacetylcholinesterase diisopropylfluorophosphate (DFP) was investigated. DFP-induced chewing movement and tremors were monitored for a period of 180 min in mu-opioid receptor knockout and wild-type mice. The autoradiographic studies of total, M1, and M2 muscarinic receptors were conducted using [(3)H]quinuclidinyl benzilate, [(3)H]pirenzepine, and [(3)H]AF-DX384 as ligands, respectively. Saline-treated mu-opioid receptor knockout and wild-type mice did not show chewing movement or tremors. Although DFP (1, 2, or 3 mg/kg, subcutaneous injection, s.c.)-induced chewing movement and tremors were shown in a dose-dependent manner, there were no significant differences in tremors induced by 1 or 2 mg/kg of DFP between mu-opioid receptor knockout and wild-type mice. There were also no significant differences in chewing movement induced by all doses of DFP between mu-opioid receptor knockout and wild-type mice. However, DFP (3 mg/kg)-induced tremors in mu-opioid receptor knockout mice were significantly increased over those in wild-type controls. Acetylcholinesterase activity in the striatum of saline-treated mu-opioid receptor knockout mice was significantly higher than that of the wild-type controls. After administration of DFP, acetylcholinesterase activity in the striatum of both mu-opioid receptor knockout and wild-type mice was significantly decreased (more than 36%, 58%, and 94% reduced at the doses of 1, 2, and 3 mg/kg, respectively) than that of their respective saline controls. M2 muscarinic receptor binding in saline-treated mu-opioid receptor knockout mice was significantly lower than that of the wild-type controls in the striatum. However, there were no significant differences in total, M1, or M2 muscarinic receptor binding in the cortex, striatum, or hippocampus of mu-opioid receptor knockout and wild-type mice after DFP administration. Our data show increased DFP-induced tremors, compensatory up-regulation of acetylcholinesterase activity, and compensatory down-regulation of M2 muscarinic receptors in the striatum of mice lacking mu-opioid receptor gene. These results suggest that the enhancement of DFP-induced tremors may be associated with the compensatory up-regulation of acetylcholinesterase activity and compensatory down-regulation of M2 muscarinic receptors in the striatum of mu-opioid receptor knockout mice.     

Altered hippocampal muscarinic M4, but not M1, receptor expression from subjects with schizophrenia.

BACKGROUND: Having shown a decrease in [3H]pirenzepine binding in the hippocampus from subjects with schizophrenia, we wished to determine whether such a change in radioligand binding was associated with changes in hippocampal mRNA for the muscarinic1 (M1) and muscarinic4 (M4) receptors in tissue from different cohorts of subjects. METHOD: The [3H]pirenzepine binding using autoradiography and in situ hybridization with oligonucleotides specific for muscarinic M1 and M4 receptors were completed using hippocampal tissue obtained postmortem from 20 control subjects and 20 subjects with schizophrenia. RESULTS: The [3H]pirenzepine binding was decreased in the dentate gyrus (p < .05), CA3 (p < .01), CA2 (p < .05), and CA1 (p < .01) regions of the hippocampus from subjects with schizophrenia. Levels of M4 mRNA varied with the diagnosis of schizophrenia (p = .01), but significant region-specific changes were not apparent. Changes in levels of mRNA for the muscarinic M1 receptor were not detected with diagnosis. CONCLUSIONS: This study suggests that decreases in hippocampal [3H]pirenzepine binding in subjects with schizophrenia are most likely associated with widespread changes in expression levels of the M4 receptor. These data further implicate the hippocampal formation in the pathology of schizophrenia.     

Characterization of muscarinic acetylcholine receptors in cultured adult skin fibroblasts: Effects of the swedish Alzheimer's disease APP 670/671 mutation on binding levels

Summary We have characterised the muscarinic receptor subtypes found in human skin fibroblasts and compared binding levels in cell lines from members of the Alzheimer's disease family with the Swedish amyloid precursor protein (APP) 670/671 mutation. Binding studies with [³H] quinuclidinyl benzilate ([³H]QNB) and the M2/M4 selective antagonist [³H](±)-5,11-dihydro-11-{[(2-[(di-propylamino)methyl]-1-piperidinyl}ethyl)amino]carbonyl}-6H-pyrido(2,3-b)(1,4) benzodiazepine-6-one ([³H]AF-DX 384) revealed the presence of a single population of muscarinic receptors on lysed fibroblast membranes. [³H]QNB binding was displaced by a number of selective muscarinic ligands with a rank order of potency: atropine>himbacine>methoctramine>(±)-p-fluoro-hexahydro-sila-difenidol hydrochloride>pirenzepine>muscarinic-toxin-3. APP 670/671 mutation carrying cell lines showed 25–35% lower levels of muscarinic receptors labelled with [³H]QNB, [³H]N-methyl scopolamine and [³H]AF-DX 384, compared to controls. This difference was not statistically significant due to large individual variation. It is concluded that muscarinic receptors on adult skin fibroblasts are predominantly of the M2 subtype. Since these cells do not possess M1 and M3 receptor subtypes, they are unlikely to provide a good model for studying muscarinic receptor regulation of APP processing.     

Decreased muscarinic receptor binding in rat brain after paradoxical sleep deprivation: an autoradiographic study

Previous work demonstrated that paradoxical sleep deprivation (PSD) leads to a decrease in yawning behavior elicited by cholinergic agonists, suggesting that a downregulation of cholinergic muscarinic receptors may occur after PSD. More recent work using intracerebral injections of muscarinic agonists has suggested a critical role for M2 receptors in paradoxical sleep. In this study [³H]AF-DX 384 was used to investigate the effects of PSD on M2-type cholinergic receptors throughout the brain using quantitative autoradiography. After 96 h of paradoxical sleep deprivation, [³H]AF-DX 384 binding was generally reduced throughout the brain, and significantly so in the olfactory tubercle (−20%), n. accumbens (−23%), frontal caudate-putamen (−16%), islands of Callejas (−20%), piriform cortex (−24%), lateral (−26%) and medial (−24%) septum, anteromedial (−19%), ventrolateral (−22%), and lateral geniculate (−15%) nuclei of thalamus, deep layers of the superior colliculus (−15%), entorhinal cortex (−12%) and subiculum (−23%). [³H]AF-DX 384 binding was reduced in pontine structures, but not to a higher degree than in other brain areas. The observed downregulation of M2-type muscarinic receptors after PSD may be causally related to the previously reported decrease in cholinergically induced behaviors after PSD.     

Characterization of muscarinic receptor subtype of rat eccrine sweat gland by autoradiography

The muscarinic cholinergic receptor of rat eccrine sweat gland was characterized using quantitative autoradiography and [3H]QNB as radioligand. The distribution of radioligand was maximal in the secretory coil. Autoradiographic competition binding studies were performed using selective antagonists to M1 (pirenzepine), M2 (AF-DX 116), and M3 (4-DAMP) and the classical nonselective antagonist atropine. pKi for pirenzepine, AF-DX 116, 4-DAMP, and atropine was 6.58, 5.47, 8.50, and 8.66 respectively indicating that the eccrine sweat gland muscarinic receptor was predominantly M3.     

Muscarinic M2 and M4 receptors in anterior cingulate cortex: relation to neuropsychiatric symptoms in dementia with Lewy bodies

Alterations in cholinergic functions have been reported to be associated with neuropsychiatric symptoms in dementia. Increased M1 muscarinic receptor binding in temporal cortex is associated with delusions in dementia with Lewy bodies (DLB) patients and increased M2/M4 receptor binding with psychosis in Alzheimer's disease. However, the relation between M2 and M4 muscarinic receptor and psychotic symptoms in DLB is unknown. The aim of this study was to measure M2 and M4 receptors in the anterior cingulate cortex in DLB and to correlate the neurochemical findings with neuropsychiatric symptoms. Muscarinic M2 and M4 receptor levels in the anterior cingulate cortex and adjacent cortex (Brodmann's area [BA] 32) were measured separately by using a radioligand binding protocol based on binding of [(3)H]AF-DX 384 in the presence and absence of dicyclomine, a potent M4 receptor antagonist. M2 receptor binding was significantly increased, while M4 receptor binding was unchanged in the cingulate cortex and BA32 of DLB patients compared with age-matched controls. Impaired consciousness was significantly associated with increased M4 binding and delusions were significantly associated with increased M2 binding. Increased M2 and M4 receptor binding in DLB was also associated with visual hallucinations. Upregulation of M2 and M4 muscarinic receptors in cingulate and adjacent cortex may thus contribute to the development of psychosis in DLB, with potential implications for treatments with drugs acting on these receptors.     

Developmental profiles of various cholinergic markers in the rat main olfactory bulb using quantitative autoradiography

The existence of possible relationships among the developmental profile of various cholinergic markers in the main olfactory bulb (OB) was assessed by using in vitro quantitative autoradiography. Muscarinic receptors were visualized with [³H]pirenzepine (muscarinic M1-like sites) and [³H]AF-DX 384 (muscarinic M2-like sites); nicotinic receptors by using [³H]cytisine (nicotinic 42-like subtype) and [¹²⁵I]α-bungarotoxin (nicotinic 7-like subtype); cholinergic nerve terminals by using [³H]vesamicol (vesicular acetylcholine transport sites) and [³H]hemicholinium-3 (high-affinity choline uptake sites). These various cholinergic markers exhibited their lowest levels at birth and reached adult values by the end of the 4–5 postnatal weeks. However, the density of presynaptic cholinergic markers and nicotinic receptors at postnatal day 2 represented a large proportion of the levels observed in adulthood, and displays a transient overexpression around postnatal day 20. In contrast, the postnatal development of cholinergic muscarinic M1-like and M2-like receptors is apparently regulated independently of the presynaptic cholinergic markers and nicotinic receptors. Two neurochemically and anatomically separate olfactory glomeruli subsets were observed in the posterior OB of the developing rat. These atypical glomeruli expressed large amounts of [³H]vesamicol- and [³H]hemicholinium binding sites without significant amounts of muscarinic M1, M2, or nicotinic α4β2 receptor binding sites. A significant density of [¹²⁵I]α-bungarotoxin binding sites could be detected only at early postnatal ages. A few olfactory glomeruli specifically restricted to the dorsal posterior OB expressed a high density of [³H]cytisine binding sites but lacked significant binding of the two presynaptic cholinergic markers used here, suggesting their noncholinergic but cholinoceptive nature. © 1996 Wiley-Liss, Inc.     

Decreased muscarinic1 receptors in the dorsolateral prefrontal cortex of subjects with schizophrenia

To test the hypothesis that muscarinic receptors are involved in the pathology of schizophrenia, we measured muscarinic(1) (M1R) and muscarinic(4)(M4R) protein and mRNA as well as [(3)H]pirenzepine binding in Brodmann's areas (BA) 9 and 40 obtained postmortem from 20 schizophrenic and 20 age/sex-matched control subjects. There was a significant decrease in [(3)H]pirenzepine binding to BA 9 (mean +/- SEM: 151 +/- 15 vs 195 +/- 10 fmol mg(-1) ETE; P< 0.02), but not BA 40 (143 +/- 13 vs 166 +/- 11 fmol mg(-1) ETE), from subjects with schizophrenia. The level of M1R protein (0.11 +/- 0.007 vs 0.15 +/- 0.008 OD; P < 0.01), but not M4R protein, was decreased in BA9 from schizophrenic subjects with neither receptor protein being altered in BA 40. The level of M1R mRNA was decreased in BA 9 (30 +/- 7.0 vs 79 +/- 14 dpm x 10(3) mg(-1) ETE, P < 0.01) and BA 40 (28 +/- 5.9 vs 99 +/- 14, P < 0.01) with schizophrenia but M4R mRNA was only decreased in BA 40 (48 +/- 6.6 vs 89 +/- 9.9, P < 0.005). These data suggest that the M1R, at least in the dorsolateral prefrontal cortex, may have a role in the pathology of schizophrenia.     

Autoradiographic localization of peripheral M1 muscarinic receptors using [H]pirenzepine

A novel antimuscarinic agent, pirenzepine, has been proposed to distinguish at least two subtypes of muscarinic receptor. M1 receptors have been designated as those displaying a high affinity for pirenzepine. Both functional and binding studies have revealed a prevalence of M1 receptors in sympathetic ganglia while autonomic effector tissues have only low densities of M1 receptors. In the present study, in vitro autoradiographic procedures have been used to localize specifically high affinity binding sites for pirenzepine (M1 receptors) in sections of guinea-pig ileum, rat superior cervical ganglion and rat submaxillary gland. The overall localization of muscarinic receptors was also studied using the non-selective antagonist, [³H]N-methylscopolamine. The highest densities of M1 receptors were found in superior cervical ganglion, sympathetic nerve bundles, myenteric ganglia and mucous secreting cells of the submaxillary gland, while lower densities were found in smooth muscle and serous secreting cells of the submaxillary gland. No area found to possess muscarinic receptors was devoid of M1 receptors.     

Characterization of muscarinic receptor subtypes in Alzheimer and control brain cortices by selective muscarinic antagonists.

Subtypes of muscarinic receptors were characterized in the frontal cortices of control and Alzheimer brains, with labelled quinuclidinyl benzilate [3H]QNB and the unlabelled muscarinic antagonists pirenzepine, AF-DX 116, hexahydro-sila-diphenidol (HHSiD), para-fluoro-hexahydro-sila-diphenidol (p-F-HHSiD) and himbacine. High and low affinity sites were observed for both pirenzepine and AF-DX 116 in human control frontal cortices. The majority (76%) of the pirenzepine binding sites showed high affinity to the muscarinic receptors (M1), while the rest of the binding sites had an affinity that was 40 times less. AF-DX 116 displayed two sets of binding sites where the high affinity AF-DX 116 (M2) sites constituted 27%, while the low affinity AF-DX 116 (non-M2 site) was 73%. A single class of binding sites was observed for HHSiD, p-F-HHSiD and himbacine in human frontal cortices. HHSiD showed an affinity in the frontal cortices that was comparable to that of the pirenzepine high affinity binding (M1) sites. The affinity of p-F-HHSiD was three times lower than that of HHSiD but similar to himbacine. A significant increase in the affinity (+ 40%) as well as in the Bmax (+ 99%) value was observed for the pirenzepine high affinity binding sites (M1) in the frontal cortices of Alzheimer brains compared to controls. Similarly, a significant increase was observed in the Bmax value (+ 60%) for the AF-DX 116 low affinity binding sites (non-M2), while no change was found for the high affinity binding sites (M2).(ABSTRACT TRUNCATED AT 250 WORDS)     

精神分裂症患者颞上回的大麻素受体密度没有显著性变化

目的 近年来研究发现,在精神分裂症患者的内源性大麻素递质系统会出现异常变化,而颞上回在精神分裂症的病理生理机制中和幻听症状密切相关.因此,对照正常人群,我们研究了精神分裂症患者颞上回大麻素CB-1受体的密度变化.方法 采用定量放射自显影技术,通过[3H]SR141716A(CB-1受体选择性拮抗剂)和[3H]CP-55940(CB-1受体激动剂)检测颞上回CB-1受体密度水平.死后脑组织由澳大利亚新南威尔士州组织资源中心提供.结果 先前研究发现,精神分裂症患者与认知功能失常相关的额前叶,前、后扣带回皮质的CB-1受体密度水平有异常改变.与此相反,本研究发现在精神分裂症患者的由[3H]SR141716A和[3H]CP-55940检测的颞上回大麻素受体密度水平和对照组比较没有显著变化.结论 我们认为颞上回大麻素CB-1受体和精神分裂症患者的发病及幻听症状无关.