Autoradiographic localization of muscarinic agonist binding sites in the rat central nervous system with (+)-cis-[H]methyldioxolane

(+)-cis-[³H]Methyldioxolane ((+)-[³H]CD), a potent muscarinic agonist, was used to label high-affinity agonist states of muscarinic receptors in thin tissue sections of the rat central nervous system. Light microscopic autoradiography of atropine-sensitive (+)-[³H]CD binding sites revealed regions of dense labeling (superior colliculus, inferior colliculus, lateral geniculate body, hypoglossal (XII) nucleus, facial (VII) nucleus, tractus diagonalis) and regions of sparse labeling (hippocampus, dentate gyrus). The inverse regional correlation between high-affinity (+)-[³H]CD states and binding sites for the muscarinic antagonists [³H]pirenzepine (r = −0.79) and (-)-[³H]quinuclidinyl benzilate (r = −0.30) underscores potentially important differences between agonist and antagonist binding to CNS tissue slices.     

In vitro and ex vivo autoradiography of the NK-1 antagonist [³H]-LY686017 in Guinea pig brain

NK-1 receptor antagonists have shown potential for the clinical treatment of chemotherapy-induced nausea and vomiting, depression and alcoholism. In a recent study, we disclosed the potential for the NK-1 antagonist, LY686017, to treat alcoholism in a clinical population. To assess whether this compound could be utilized as a platform for a brain imaging ligand, we evaluated the binding of [³H]-LY686017 to sections of guinea pig in vitro. In these studies, [³H]-LY686017 bound with a distribution and pharmacology consistent with the NK-1 receptor. Using sections through the region of the caudate nucleus, we obtained a K_d of 0.34 nM and a B_max of 31.37 fmoles/mg tissue. Based on its high potency and low nonspecific binding in vitro, we initiated studies to evaluate the radioligand as a tool to measure in vivo receptor occupancy. In initial studies, 25 microCi of [³H]-LY686017 was administered via an indwelling jugular catheter and accumulation of radioactivity in the caudate (NK-1 containing tissue) and cerebellum (low NK-1 expression) were assessed. The ratios of caudate to cerebellum radioactivity were optimal 2 h after radioligand administration so this time point was used for subsequent studies. To assess the pharmacological specificity of the radioactivity accumulation, we administered various doses of Aprepitant, a potent NK-1 antagonists 1 h prior to intravenous administration of [³H]-LY686017. Aprepitant produced a dose-dependent reduction in radioactivity in the caudate with an approximate 70% reduction at 10 mg/kg. To image NK-1 receptors, 100 microCi of [³H]-LY686017 was administered and the brains sectioned for autoradiography. In these studies, a characteristic distribution on NK-1 receptors was observed. Based on these results, LY686017 should serve as a suitable chemical platform for future imaging ligand development.     

Increase in thalamic binding of [C]PE2I in patients with schizophrenia: A positron emission tomography study of dopamine transporter

Previous in vivo imaging studies reported no difference in dopamine transporter (DAT) bindings in the striatum between control subjects and patients with schizophrenia. However, as the signals of radioligands with moderate affinity were insufficient for allowing the evaluation of small amounts of DAT, DAT binding in extrastriatal regions has not been determined. Positron emission tomography scanning using [¹¹C]PE2I was performed on eight patients with schizophrenia and twelve normal control subjects. Binding potential (BP_ND) for DAT in the caudate, putamen, thalamus and substantia nigra was calculated, using the cerebellum as reference region. In patients with schizophrenia, clinical symptoms were evaluated by Positive and Negative Syndrome Scale (PANSS). BP_ND in the thalamus of patients with schizophrenia was significantly higher than in control subjects (P = 0.044). In patients with schizophrenia, there were significantly positive correlations between BP_ND in the thalamus and total (r = 0.75), positive (r = 0.78) and negative PANSS scores (r = 0.82). Altered DAT in the thalamus might be related to the pathophysiology and clinical symptoms of schizophrenia.     

Autoradiographic localization of α5 subunit-containing GABAA receptors in rat brain

Multiple subtypes of GABA_A receptors are expressed in the rat central nervous system (CNS). To determine the distribution and proportion of α5 subunit containing receptors, quantitative autoradiographic analyses were performed with both [³H]L-655,708 and [³H]Ro15-1788, an α5 selective and a non selective benzodiazepine binding site ligand, respectively. High densities of [³H]L-655,708 binding sites were observed in hippocampus and olfactory bulb, where α5 receptors accounted for 20–35% of total [³H]Ro15-1788 binding sites. Low levels of [³H]L-655,708 sites were associated with the cortex as well as amygdala, thalamic, hypothalamic and midbrain nuclei. These observations indicate that although [³H]L-655,708 binding sites have an overall low expression in rat CNS, they may contribute significantly to GABAergic inhibition in specific brain regions.     

Maximal densities of μ, δ, and κ receptors are differentially altered by focal cerebral ischaemia in the mouse

Though opioids are known to have neuroprotective properties, little information is available on the functional state of opioidergic receptors following focal cerebral ischaemia. The present study investigated the evolution of the B_max and K_d for [³H]DAMGO, [³H]DADLE, and [³H]U69,593, respectively, for the μ, δ, and κ opioidergic receptors after permanent focal cerebral ischaemia in mice. While the various K_d were unchanged, μ and δ B_max values were precociously decreased in frontoparietal cortices, earlier than κ receptors, reflecting infarct extension with time. The B_max values for μ and δ receptors were also altered in non-infarcted tissues, such as tissues at risk (e.g., temporal auditory cortex) and exofocal (e.g., contralateral and non-infarcted) cortices. These results suggest that, in non-infarcted areas, the observed changes reflect functional modifications to focal ischaemia.     

Cognitive enhancing effects of an AMPA receptor positive modulator on place learning in mice

This study presents an in vivo investigation of the arylpropylsulfonamide α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor positive modulator (R,R)-N,N-(2,20-[biphenyl-4-40-diyl]bis[propane-2,1-diyl])dimethanesulfonamide (PIMSD). The pharmacokinetics of the drug were examined in male C57BL/6J mice and the drug concentration in blood plasma determined after subcutaneous injection of 1 mg/kg b.w. This analysis revealed a rapid increase of the plasma concentration, peaking within 30 min after administration with a T_1/2 of approximately 30 min and a peak plasma concentration of about 2 μM. Analysis of brain tissue homogenates also indicated blood-brain barrier permeability of the compound. Cognitive enhancing effects of the drug were then studied on place learning in male C57BL/6J mice in a water maze. In order to elucidate the potential positive effects of PIMSD on spatial learning the muscarinergic antagonist scopolamine was utilized, which is known to impair spatial learning ability. The mice were divided into four groups and subjected to two sequential subcutaneous injections administered 25 min prior to behavioural testing: (1) vehicle/vehicle; (2) PIMSD/vehicle; (3) scopolamine/vehicle; (4) PIMSD/scopolamine. PIMSD at a dose of 3 mg/kg b.w. was able to partially reverse the impairment given by 0.5 mg/kg b.w. scopolamine. These results suggest that arylpropylsulfonamides such as PIMSD may have a therapeutic use in the enhancement of cognitive function and support the hypothesis that AMPA receptor potentiation is one mechanism that can be targeted for diseases of cognitive impairment.     

Muscarinic cholinergic receptors in the human spinal cord: differential localization of [H]pirenzepine and [H]quinuclidinylbenzilate binding sites

The localization of muscarinic cholinergic receptor subtypes was studied in the human spinal cord using in vitro labelling of cryostat sections with [³H]quinuclidinylbenzilate (QNB) and [³H]pirenzepine (PZ) followed by autoradiography. The highest densities of [³H]QNB binding were localized in laminae II (substantia gelatinosa) and IX (motor neurons); in contrast, the highest density of [³H]PZ binding was localized to lamina II where the binding density was 22—32% higher than in lamina IX. These results suggest that the M₁ and M₂ muscarinic cholinergic receptor subtypes may be differentially localized in sensory and motor regions of the human spinal cord.     

SAT-1 -1415T/C polymorphism and susceptibility to schizophrenia

Patients suffering from psychosis show increased blood and fibroblast total polyamine levels. Spermidine/spermine N1-acetyltransferase (SSAT-1) and its coding gene (SAT-1) are the main factors regulating polyamine catabolism. The aim of the present study was to examine the association between the SAT-1 -1415T/C single nucleotide polymorphism (SNP) and schizophrenia. A case-control design was used in order to compare the genotypes for the SNP between schizophrenia patients (n = 180, 83 females and 97 males), other non-psychotic psychiatric patients (n = 413, 256 females and 157 males), and healthy controls (n = 251, 101 females and 150 males).     

Altered platelet calsequestrin abundance,Na/Ca exchange and Ca signaling responses with the progression of diabetes mellitus

Introduction

Downregulation of calsequestrin (CSQ), a major Ca^2 + storage protein, may contribute significantly to the hyperactivity of internal Ca^2 + ([Ca^2 +]_i) in diabetic platelets. Here, we investigated changes in CSQ-1 abundance, Ca^2 + signaling and aggregation responses to stimulation with the progression of diabetes, especially the mechanism(s) underlying the exaggerated Ca^2 + influx in diabetic platelets.

Materials and methods

Type 1 diabetes was induced by streptozotocin in rats. Platelet [Ca^2 +]_i and aggregation responses upon ADP stimulation were assessed by fluorescence spectrophotometry and aggregometry, respectively. CSQ-1 expression was evaluated using western blotting.

Results

During the 12-week course of diabetes, the abundance of CSQ-1, basal [Ca^2 +]_i and ADP-induced Ca^2 + release were progressively altered in diabetic platelets, while the elevated Ca^2 + influx and platelet aggregation were not correlated with diabetes development. 2-Aminoethoxydiphenyl borate, the store-operated Ca^2 + channel blocker, almost completely abolished ADP-induced Ca^2 + influx in normal and diabetic platelets, whereas nifedipine, an inhibitor of the nicotinic acid adenine dinucleotide phosphate receptor, showed no effect. Additionally, inhibition of Na⁺/Ca^2 + exchange induced much slower Ca^2 + extrusion and more Ca^2 + influx in normal platelets than in diabetic platelets. Furthermore, under the condition of Ca^2 +-ATPase inhibition, ionomycin caused greater Ca^2 + mobilization and Ca^2 + influx in diabetic platelets than in normal platelets.

Conclusions

These data demonstrate that platelet hyperactivity in diabetes is caused by several integrated factors. Besides the downregulation of CSQ-1 that mainly disrupts basal Ca^2 + homeostasis, insufficient Na⁺/Ca^2 + exchange also contributes, at least in part, to the hyperactive Ca^2 + response to stimulation in diabetic platelets.     

[H]Nemonapride Binding in Human Caudate and Putamen

The binding of [³H]nemonapride to human postmortem caudate and putamen tissue was autoradiographically investigated using several antipsychotic drugs. Saturation experiments revealed a single population of binding sites (dissociation constant (K_D) 0.38 ± 0.01 nM, and total binding capacity (B_MAX) 55 fmol/TE). Prototypic dopamine (DA) receptors antagonists displaced [³H]nemonapride in a monophasic manner. The order of displacement potency was expected for DA D₂-like receptors: spiperone > (+)butaclamol ≥ chlorpromazine > (−)sulpiride > ketanserin. Displacement with serotonergic antagonists suggests that in human caudate and putamen tissue [³H]nemonapride may have a very low affinity serotonergic component. However, [³H]nemonapride displays a high affinity and selectivity for DA D₂-like receptors and should make it a preferred compound for tritium-based autoradiography.     

Crucial role of kainate receptors in mediating striatal kainate injection-induced decrease in acetylcholine M1 receptor binding in rat forebrain

We investigated the roles of kainate-, α-amino-3-hydroxy-5-methylisoxazol-4-propionate (AMPA)- and N-methyl- -aspartate (NMDA)-receptors in mediating striatal kainate injection-induced decrease in the binding of acetylcholine M₁ receptors in rat forebrain. After unilateral intrastriatal injection of kainate (4 nmol), the bindings of [³H]kainate (10 nM), [³H]MK-801 (4 nM) and [³H]pirenzepine (4 nM) to the rat ipsilateral forebrain membranes declined, reaching the lowest on day 2 to 4 and recovering on day 8. Saturation binding studies, performed on day 2 post-injection, showed that kainate (1, 2, 4 nmol) dose-dependently decreased B_max and K_d of the three ligands. (+)-5-Methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine (MK-801), a selective NMDA receptor channel blocker, antagonised (from a dose of 4 nmol) kainate-induced decreases in the bindings of [³H]kainate (up to 20%), [³H]MK-801 (up to 90%) and [³H]pirenzepine (up to 70%). In contrast, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), a selective non-NMDA receptor antagonist, almost completely abolished (from a dose of 12 nmol) kainate-induced decreases in the bindings of all the three ligands (up to 95–98%). Cyclothiazide, a selective potentiator that enhances AMPA receptor-mediated responses, significantly enhanced (from a dose of 4 nmol) kainate-induced decrease in the binding of [³H]kainate but not that of [³H]pirenzepine or [³H]MK-801. In summary, these results indicate that striatal kainate injection-induced decrease in the binding of acetylcholine M₁ receptors in rat forebrain is dependent on activation of kainate receptors and, to a certain extent, a consequent involvement of NMDA receptors. These and previous studies provide some evidence showing that kainate receptors might play a crucial role in regulating excitatory amino acids (EAA)-modulated cholinergic neurotransmission in the central nervous system (CNS).     

I(4), a new synthetic sulfonylurea compound, inhibits the action of TXA(2)in vivo and in vitro on platelets and aorta vascular smooth muscle

Introduction

1-[4-[2-(4-Bromobenzene-sulfonamino)ethyl]phenylsulfonyl]-3-(trans-4-methylcy-clohexyl)urea(I₄, CAS865483-06-3); a totally synthetic new sulfonylurea compound, combining the hypoglycemic active structure of Glimepiride (CAS 93479-97-1) and anti-TXA₂ receptor (TP) active structure of BM-531(CAS 284464-46-6), was designed and synthesized. Its effects on TXA₂ synthesis and TP have not been reported yet.

Aim

To study the inhibitory effects of I₄ and its mechanisms of action on TXA₂ and TP.

Methods

Platelet aggregation studies were performed on human platelet, rat whole blood platelet and rabbit platelet, platelets aggregation was induced by TP agonist U-46619(stable analog of TXA₂, CAS 56985-40-1). Plasma TXB₂ and 6-keto-prostaglandin F_1α (6-keto-PGF_1α) were used as markers to determine the effect of I₄ on thromboxane synthesis. Fluo-3-AM was used to measure the cytosolic Ca^2 + concentrations ([Ca^2 +]_i) in rabbit platelet. Aorta rings with and without endothelium were prepared and aorta contraction was induced by U-46619. A model of type 2 diabetes mellitus was established by intraperitoneal injection of low dose of streptozocin to rats fed a high-calorie diet. Both normal rats and type 2 diabetic rats were used to assay the inhibitory effect of I₄ on platelet aggregation induced by U-46619.

Results

I₄ exhibited a higher inhibitory potency than Glimepiride on U-46619 induced platelet aggregation in vitro and in vivo. I₄ increased the ratio of plasma PGI₂/TXA₂ and decreased [Ca^2 +]_i release from platelet internal stores. In addition, I₄ presented a vasorelaxant activity on isolated rat aorta contraction induced by U-46619.Oral administration of I₄ (1 ~ 10 mg/kg) markedly and dose-dependently inhibited platelet aggregation in both normal rats and type 2 diabetic rats.

Conclusion

I₄ significantly inhibited platelet aggregation induced by U-46619 in vitro and in vivo, and rat aorta contraction. It probably acts by partly blocking TXA₂ action, decreasing the platelet intracellular Ca^2 +, and increasing the PGI₂/TXA₂ ratio.     

The novel anticonvulsant MK-801: a potent and specific ligand of the brain phencyclidine/gd-receptor

MK-801 (5-methyl-10, 11-dihydro-5H-dibenzo[a,d]cyclohepten-5, 10-imine maleate) is a novel anticonvulsant agent reported to antagonize certain N-methyl-spd-aspartate (NMDA)-mediated effects non-competitively. The question arises of the mechanism underlying the anti-NMDA and anticonvulsant effects of MK-801. In the present study MK-801 is shown to be an extremely potent inhibitor of the binding of N-[³H](1-[2-thienyl]cyclohexy)piperidine) ([s3H]TCP to brain phencyclidine (PCP)/δ-receptors. It is IC₅₎ value of 3.8 ± 0.8 nM in this assay ranks it as the most potent known ligand of brain PCP/δ-receptors. Addition of MK-801 altered the apparent K_d but not the apparent B_max values for [³H]TCP binding, indicating a competitive interaction. The specificity of action of MK-801 is supported by the finding that MK-801 strongly inhibited the binding of (+)-N-[³H]allylnormetazocine ((+)-[³H]SKF 10.047) to the PCP/δ-receptor but its effect on (+)-[³H]SKF 10.047 binding to the non-PCP, haloperidol-sensitive δ-binding site was weaker by several orders of magnitude. Furthermore, MK-801 exerts PCP-like antagonistic effects upon NMDA-induced [³H]norepinephrine release. These findings support the concept that the anticonvulsant and anti-NMDA effects of MK-801 result from its being the most potent known ligand of PCP/δ-receptors.     

Two binding sites for [3H]PBR28 in human brain: implications for TSPO PET imaging of neuroinflammation

[¹¹C]PBR28, a radioligand targeting the translocator protein (TSPO), does not produce a specific binding signal in approximately 14% of healthy volunteers. This phenomenon has not been reported for [¹¹C]PK11195, another TSPO radioligand. We measured the specific binding signals with [³H]PK11195 and [³H]PBR28 in brain tissue from 22 donors. Overall, 23% of the samples did not generate a visually detectable specific autoradiographic signal with [³H]PBR28, although all samples showed [³H]PK11195 binding. There was a marked reduction in the affinity of [³H]PBR28 for TSPO in samples with no visible [³H]PBR28 autoradiographic signal (K_i=188±15.6 nmol/L), relative to those showing normal signal (K_i=3.4±0.5 nmol/L, P<0.001). Of this latter group, [³H]PBR28 bound with a two-site fit in 40% of cases, with affinities (K_i) of 4.0±2.4 nmol/L (high-affinity site) and 313±77 nmol/L (low-affinity site). There was no difference in K_d or B_max for [³H]PK11195 in samples showing no [³H]PBR28 autoradiographic signal relative to those showing normal [³H]PBR28 autoradiographic signal. [³H]PK11195 bound with a single site for all samples. The existence of three different binding patterns with PBR28 (high-affinity binding (46%), low-affinity binding (23%), and two-site binding (31%)) suggests that a reduction in [¹¹C]PBR28 binding may not be interpreted simply as a reduction in TSPO density. The functional significance of differences in binding characteristics warrants further investigation.     

The distribution and function of DL-[H]2-Amino-4-Phosphonobutyrate binding sites in the rat striatum

The binding of the glutate-like radioligand,DL-[³H]2-amino-4-phosphhonobutyrate (DL-[³H]APB), to L-glutamate-sensitive sites in the rat striatum was investigated. A single, saturable population of binding sites, indistinguishable from that characterized previously on rat whole brain synaptic membranes, was identified. The effects of specific lesions of the striatum: (a) decortication; (b) striatal injection of kainic acid; and (c) 6-hydroxydopamine injections into the substantia nigra, were also examined. SpecificDL-[³H]APB binding in the striatum was elevated significantly following decortication. An increase in the number of binding sites was found to be responsible for this enhancement in binding. Lesions of the postsynaptic tartets of corticostriatal fibres reduced the number of DL-[³H]APB binding sites in the striatum without affecting binding site affinity. This finding suggests thatL-APB sensitive excitatory amino acid receptors are located predominantly on membranes derived from structures postsynaptic with regard to the glutamatergic innervation. The possible physiological role of these receptors was examined using an in vitro release technique. BothL-glutamate and L-APB were found to facilitate potassium evoked [³H]dopamine release from striatal slices. This finding supports the proposed existence of functional acidic amino acid receptors on dopaminergic terminals in the striatum. These receptors may play an important role in the control of motor function.     

In vitro and in vivo evidence for the existence of presynaptic muscarinic cholinergic receptors in the rat hippocampus

The intrahippocampal injection of kainic acid cleared 50% of muscarinic receptors and favored the detection of a further 20% loss in hippocampal presynaptic muscarinic receptors produced by electrolytic lesion of the medial septal nucleus as determined by Scatchard analysis of the saturation isotherms of [³H]dexetimide binding. In accordance, a decrease of about 20% in the in vivo accumulation of [³H]dexetimide in the hippocampus was found in animals lesioned in the medial septal nucleus. This effect occurred at both the dose of 5 μg/kg and at the saturating dose of 100 μg/kg of [³H]dexetimide. The results suggest that the loss was due to decreased receptor number rather than decreased receptor affinity.     

Noninvasive quantification of metabotropic glutamate receptor type 1 with [11C]ITDM: a small-animal PET study

Because of its role in multiple central nervous system (CNS) pathways, metabotropic glutamate receptor type 1 (mGluR1) is a crucial target in the development of pharmaceuticals for CNS disorders. N-[4-[6-(isopropylamino)-pyrimidin-4-yl]-1,3-thiazol-2-yl]-N-methyl-4-[¹¹C]-methylbenzamide ([¹¹C]ITDM) was recently developed as a positron emission tomography (PET) ligand for mGluR1. To devise a method for measurement of the binding potential (BP_ND) of [¹¹C]ITDM to mGluR1, reference tissue methods aimed at replacing measurement of the arterial input function are desirable. In this study, we evaluated a noninvasive quantification method of mGluR1 with [¹¹C]ITDM, demonstrating its accuracy using Huntington disease model R6/2 mice. The BP_ND measurements based on the Logan reference (Logan Ref) method have closely approximated that based on the arterial input method. We performed PET analysis with Logan Ref to assess its accuracy in quantifying the decline of mGluR1 expression in R6/2 mice. Significant decreases in BP_ND values in R6/2 mice were detected in cerebellum, thalamus, striatum, and cingulate cortex. We compared autoradiographs of R6/2 mouse brain sections with immunohistochemical images, and found a close correlation between changes in radioactive signal intensity and degree of mGluR1 expression. In conclusion, [¹¹C]ITDM-PET is a promising tool for in vivo quantification of mGluR1 expression.     

Acute and long-term effects of 17β-estradiol on Gi/o coupled neurotransmitter receptor function in the female rat brain as assessed by agonist-stimulated [S]GTPγS binding

Estrogens exert effects on mood, mental state, memory and other central nervous system (CNS) functions by modulating neurotransmitter receptor systems in the brain. Studies were designed to investigate the effect of 17β-estradiol (E₂) on agonist-stimulated [³⁵S]GTPγS binding in membranes to assess the first step in the intracellular signal transduction cascade in a functional assay following: (1) an acute, one-time bolus subcutaneous injection, or (2) 14-day continuous exposure by a slow-release pellet implanted subcutaneously. In rats treated with E₂ acutely, the maximal response produced by activation of serotonin_1A (5-HT_1A) receptors was decreased 25% in the hippocampus, cortex, and amygdala. Similarly, acute E₂ administration desensitized 5-HT_1B and GABA_B receptors in hypothalamus and cerebellum, respectively, and cannabinoid receptors in hippocampus and cortex. Although the maximal responses were decreased, acute E₂ treatment did not alter the EC₅₀ of any of the aforementioned receptors. The incubation of membranes prepared from the cortex of ovariectomized (OVX) rats with E₂ (1 μM) in vitro did not alter 5-HT_1A or cannabinoid receptor-mediated [³⁵S]GTPγS binding. By contrast to acute treatment in vivo, 14-day E₂ administration to OVX rats did not alter the maximal responses produced by activation of 5-HT_1A, 5-HT_1B, GABA_B, or cannabinoid receptors in any of the brain regions examined. Thus, it is concluded that acute E₂ administration in vivo modulates multiple G_i/o coupled receptors in various regions of the female rat brain. Because these effects are observed only in vivo, it is concluded that cytosolic, nuclear and/or extraneuronal factors are required.     

Frontal decortication decreases the affinity ofN-(1-[2-thienyl]cyclohexyl)[H]piperidine binding to rat striatum Frontal decortication; Striatum

Bilateral ablation or transection of the corticostriatal pathways of the rat causede a reduction inN-(1-[2-thienyl]cyclohexyl)-[³H]piperidine ([³H]TCP) binding to the striatum at 5–7, but not 3 and 14–28, days postlesion with a persistent decrease in striatal glutamate content 3–28 days after the decortication. This reduction was found to be due to an increase inK_d without changes inB_max of the [³H]TCP binding. The present binding suggest that interruption of striatal glutamatergic transmission following frontal decortication may produce a temporal reduction in the affinity of phencyclidine receptor in th striatum.