bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular orbital calculations of metal ion interaction with nucleic acid bases. I. Binding of Cu(II) with adenine, guanine, uracil, and cytosine
Authors: Kothekar V. , Dutta S.
Published: December 2004

The reaction of the transition metal ion Cu(II) with nucleic acid bases—adenine, guanine, uracil, and cytosine—has been investigated by conformation energy calculations (CEC) and molecular orbital (MO) methods. Various binding sites, e.g., N7–C6NH2, N7–C6O, N3‐N9, and N1 in purines and N3 and O8 in pyramidines, have been considered. It was found that the energy minima for different binding sites had different values. In addition to the energy minima in the nucleic acid base plane, we have observed out‐of‐plane energy minima, differing in energy by a few kcal/mol in most of the cases. The MO calculations were performed on the most favorable planar positions obtained. It was found that the presence of Cu(II) alters the charge distribution pattern of practically all the atoms of nucleic acid bases. Its main effect is to withdraw electrons from the negatively charged nitrogens and positively charged carbons. The oxygen charge did not alter significantly. The results are compared with the experimental electron spin resonance and x‐ray diffraction studies and their biological significance is discussed.
The antisymmetrized product of weak nonorthogonal geminals
Authors: Lyast I. Ts.
Published: December 2004

Most commonly the nonorthogonality of geminals is weakly expressed so that the exchange and overlap integrals ζ(η), φ(η) are negligible for large exchange parameters η. The conditions which allow the terms with large η to be discarded are considered. The integrals ζ(η), φ(η) are derived for η = 2, 3, 4.
On the non‐existence of maxima in variational computations containing non‐linear parameters
Authors: Tal Yoram , Katriel Jacob
Published: December 2004

The homogeneity properties of the kinetic and potential energy operators are used to obtain expressions for the second derivatives of the energy expectation value. These are used to demonstrate that in atoms as well as in molecules in the neighborhood of the equilibrium geometry the variational energy cannot have maxima with respect to the non‐linear parameters.
On the concept of “Partitions” in the perturbation theory of n‐electron systems
Authors: Schmidt H. M.
Published: December 2004

This paper deals with the perturbation theory of an n‐electron Hamiltonian of the general form H = ∑n ƒ(i) + λ∑n g(i, j) = H (f, g; n). In comparison to the Brueckner–Goldstone diagrammatic perturbation theory, we adopt the more general standpoint of admitting, for the construction of an n‐particle state, component states of 1, 2, 3, and more particles [O. Sinanoglu, Phys. Rev. 122, 493 (1961) and C. D. H. Chisholm and A. Dalgarno, Proc. R. Soc. (London) Sec. A 292, 264 (1966)]. We show that this leads to the concept of a “partition” of a perturbational eigenstate (or energy) of H. A “partition” is a natural decomposition which: (i) is finite; (ii) relates the eigenvalue problem of the system H = H (f, g; n) to those of certain subsystems H (f, g; n1)(n1 < n); (iii) uses “nonseparable” components. We domonstrate (under the preliminary assumption of “strict” nondegeneracy) the second‐order energy to possess a “partition.” The components therein are second‐order energies of two‐ and three‐particle states. The proof uses an extension of Racah's concept of the fractional‐parentage expansion.
Four‐dimensional density and energy density functional
Authors: Kryachko Eugene S.
Published: December 2004

The relations based on an external one‐electron operator V(r) are examined from two view‐points, i.e., from the Hohenberg–Kohn approach and the four‐dimensional density concept introduced by Wilson and Frost, and extensively studied by Parr and Politzer. The object being to obtain, with the help of the Hellmann–Feynman theorem, new formulas for the energy of atoms and molecules, and to discuss the construction of the universal energy density functional on the basis of the four‐dimensional density.
Bonding in alkali metal homonuclear diatomics
Authors: Pelissier Michel , Davidson Ernest R.
Published: December 2004

An analysis of the factors that contribute to the stability of the bond between alkali metal atoms is made by using nonorthogonal configuration interaction. Beyond the orbital size, the overlap of the valence orbitals of one atom with the core orbitals of the other accounts for most of the difference between the hydrogen molecule and the alkali metal diatomics. It is shown that the valence bond description does not provide a satisfactory description in any case except for the hydrogen molecule, and valence electron correlation using the p‐type valence orbitals is essential.
Calculation of bound‐state energies from a variational functional method
Authors: Fernández Francisco M. , Arteca Gustavo A. , Castro Eduardo A.
Published: December 2004

A variational functional method is improved and generalized in order to obtain approximate bound‐state energies of a wide variety of quantum‐mechanical systems. Calculations on the discrete spectrum of the hydrogen atom in a magnetic field and the bounded harmonic oscillator show that the procedure is very promising.
A modified PCILO framework using the CNDO/Boyd–Whitehead parametrization
Authors: Lochmann R. , Weller Th. , Köhler H.‐J.
Published: December 2004

The CNDO/BW modification of the CNDO/2 approximation was used within the PCILO framework. It was shown on some significant examples that all the good results of the original PCILO‐CNDO/2 method can be reproduced by the modified version PCILO‐CNDO/BW at least. Thus, preserving the quality of its results a computer‐expense‐reduced PCILO method is proposed for calculations on large molecular systems.
Hydration of GABA and of the GABA·ZN2+ complex: A Monte Carlo simulation study
Authors: Leś Andrzej , Grabowski Sławomir
Published: December 2004

With empirical and theoretical atom–atom potentials the GABA·nH2O, n = 25, 192 and GABA·Zn2+ · nH2O, n = 25, 50, 100 complexes are simulated at 298.15 K by the Monte Carlo technique. The results show that the carboxyl group of GABA coordinates six water molecules. Two geometries of the GABA·Zn2+ complex, corresponding to the “direct” and “through‐water” interaction of Zn2+ with the carboxyl group of GABA were found. For the latter interaction a GABA·Zn2+ · 6H2O complex was found whereas the hydration of the former interaction leads to a GABA·Zn2+ · 5H2O complex. Here the carboxyl group of GABA displaces only one water molecule in the first hydration shell of Zn2+. Energetically the “direct” and “through‐water” geometries seem to be competitive, the former being slightly favored.
Iterative degenerate perturbation theory
Authors: Golovko V. F.
Published: December 2004

A fairly general degenerate perturbation theory has been considered which involves two versions, i.e., the Rayleigh‐Schrodinger and Brillouin‐Wigner treatments. The simple recursive formulas have been found for effective Hamiltonians which allow one to split the degenerate energy levels in any orders of this theory.
Theoretical approach of the chemical reactivity: The SN2 reaction
Authors: Serre Josiane
Published: December 2004

In this survey paper the different possible theoretical ways of treating the SN2 reaction are explained. It is shown that, in the future, experience and theory will very likely complement each other.
Charge distributions and chemical effects. XXXIV. Concepts involved in an approximate, but accurate, description of bond energies
Authors: Fliszár Sándor
Published: December 2004

The concepts underlying the definition of bond energies in terms of potentials at the nuclei are outlined. The theory is rooted, first, in a definition of the energy, Ei, of “atom” i in the molecule in terms of the potential energy, V(i, mol), of nucleus Zi in the field of all the electrons and nuclei of the molecule: Ei = K V(i, mol). The K parameter, which is not required to be a constant in the derivation of the energy expression describing the contribution of an ij bond, turns out to be virtually constant for each atomic species—a situation which is exploited in numerical applications. Second, the Hellmann—Feynman theorem is applied in the calculation of the derivative, δΔE/δZi, of the atomization energy, ΔE, using (i) the exact quantum‐chemical definition of ΔE and (ii) the view that ΔE is the sum of bond energy contributions, εij, plus a small interaction between nonbonded atoms. The individual bond energies derived in this manner necessarily depend on local charges at the bond‐forming atoms. Numerical applications illustrate how this new bond‐energy formula provides a simple link between typical saturated, olefinic, acetylenic, and aromatic hydrocarbons.
Preliminary results of a theoretical ab initio model study of adsorption on ionic crystals
Authors: Bourg M.
Published: December 2004

The adsorption of metals on ionic surfaces takes place on preferential sites and is affected by the presence of defects. In order to provide some theoretical indication concerning electronic energy changes connected with these effects, we have extended previous work [A. Julg and M. Bourg, J. Phys. Lett. 43, L243 (1982)] where Lin clusters embedded in a matrix simulated by point charges had been studied by STO‐6G (G‐70) calculations. We have treated an Li2 molecule in the presence of an fcc lattice of positive and negative point charges placed at the distances characteristic of an LiF crystal: The perfect surface as well as steps and point defects have been thus simulated. In this article we briefly describe the results obtained.
A model of the primary process in photosynthesis
Authors: Avery John
Published: December 2004

The arrangement of membrane‐bound pigments, proteins, and lipids in the thylakoids of higher plants is described, and the role of the membrane in preventing the back‐reaction is discussed. The photosynthetic bacterium halobacterium halobium is also described. A simplified quantum‐mechanical picture of the primary process in photosynthesis is presented, and the mechanism of electron‐hole separation in this picture is compared with the corresponding mechanism in a silicon solar cell. An appendix discusses the application of Frenkel exciton theory to the antenna effect.
Similarity transformation of the ab initio density matrix
Authors: Singh O. P. , Yadav J. S.
Published: December 2004

Bond orders and hybrid populations have been calculated from the density matrix localized in molecular space using similarity transformation for some fluorobenzene with the minimal basis set using Gaussian series of program. The ab initio bond orders and hybrid populations have been compared with the semiempirical calculations on this set of molecules. Also, these bond orders have been used in Coulson's bond order‐bond length relationship to estimate bond lengths. The present calculations suggest that the qualitative predictions of molecular geometries are possible from these bond orders.
The pseudopotential‐CI study of the interaction between ethylene and metal atoms, metal Oxides, and their cations (Me = Be, Mg, and Zn)
Authors: Witko Malgorzata , BonačIć‐Koutecký Vlasta
Published: December 2004

Potential energy curves for the lowest singlet and triplet states of Me + C2H4, Me+ + C2H4, MeO, MeO + C2H4, and (MeO + C2H4)+ systems for Me = Be, Mg, and Zn have been determined employing PP‐MRD‐CI or an all electron MRD‐CI procedure. A binding interaction in the ground state has been found for oxides, all cation systems, and the BeO + C2H4 system. In the cases of MgO + C2H4 and ZnO + C2H4, only low lying excited states exhibit attractive interactions. Among three oxides considered, BeO is less pronounced biradically than MgO and ZnO. In order to obtain a binding interaction between an oxide and the olefin in the ground state, the p orbital of the metal must be sufficiently involved in binding.
High spatial resolution Auger linescans across heterogeneous chemical edges by Monte Carlo calculation
Authors: Tuppen C. G. , Davies G. J.
Published: December 2004

Previous calculations have shown that Auger yields increase at chemical edge/free space interfaces. In this paper we consider the edge formed by a well defined thin film on a substrate of different chemical composition. Two systems have been investigated: Au and Si and Al on Si. Linescans are presented for a number of different electron beam configurations and show significant features attributable to an edge effect. These effects are explained in terms of the different layer materials and their corresponding backscatter coefficients.
Chemical synapses, particle arrays, pseudo‐gap junctions and gap junctions of neurons and glia in the buccal ganglion of Helisoma
Authors: Berdan R. C. , Shivers R. R. , Bulloch A. G. M.
Published: December 2004

The nervous system of the snail, Helisoma trivolvis, has been utilized for a wide range of studies of neuronal plasticity; however, the ultrastructural features of this tissue were perviously unknown. The present study examined the nature of synaptic interactions of neurons and glia and considered several plasma membrane specializations of these cells. The symmetrical pair of buccal ganglia consisted of a ring of unipolar neurons surrounding a central neuropil. The neurons were separated by two morphologically distinct types of glia: type I were most numerous and possessed an electron‐dense homogenous cytoplasm, whereas type II glia were of lower electron density, possessed a heterogenous cytoplasm, and appeared to be phagocytic. Gap junctions were abundant between glia and were occasionally found between neuronal processes, including those of neurons 19 injected with horseradish peroxidase (HRP). Comparison of neuron and glial gap junction widths (16.4 and 17.6 nm, respectively) in thin sections and their intramembrane particle diameters (13.1 and 13.7 nm, respectively) by freeze fracture, did not elucidate significant differences. A heterogenous population of putative chemical synapses, similar to those reported in other molluscs, was also observed between axonal collaterals in the neuropil. Additionally, examination of freeze‐fractured neuropil revealed rhombic arrays of particles localized on neuronal membranes; these arrays do not appear to form intercellular junctions but may represent postsynaptic receptor sites. Freeze fracture also revealed small, square arrays consisting of 7–9 nm diameter particles on glial membranes which may correspond to pentalaminar membrane contact (pseudo‐gap junctions) seen in thin sections between glia situated around dilated extracellular spaces (lacunae).
Transplantation of cultured human adrenal chromaffin cells into 6‐hydroxydopamine‐lesioned rat brain
Authors: Kamo Hisaki , Kim Seung U. , McGeer Patrick L. , Tago Hisao , Shin Doo H.
Published: December 2004

Adult young rats were subjected to a unilateral 6‐hydroxydopamine lesion of the nigrostriatal dopamine pathway and then given intrastriatal grafts of human fetal adrenal chromaffin cell cultures. Amphetamine‐induced ipsiversive turning behavior in the lesioned rats was largely reversed in four of eight rats given such transplants when tested at 1.5 and 4.5 months post‐transplantation. Two rats showed a transient recovery at 1.5 months followed by deterioration at 4.5 months, while two other rats showed continuous deterioration. Six rats given sciatic nerve grafts as controls all showed deterioration from the pretransplantation levels. Catecholamine fluorescent and immunohistochemical examination of chromaffin‐cell‐transplanted brains demonstrated neurons and neuronal processes positive for catecholamines or tyrosine hydroxylase in the transplanted area. This transplantation of cultured human fetal cells to an animal model may provide the necessary basic experimental system for assessing the possible utility of human neuronal transplants.
Neonatal deafferentation prevents normal expression of synaptic vesicle antigens in the developing rat superior cervical ganglion
Authors: Greif Karen F. , Trenchard Holly
Published: December 2004

The effect of neonatal deafferentation of the rat superior cervical ganglion (SCG) on the expression of two synaptic vesicle proteins was studied to assess the role of transsynaptic influences in the regulation of these neural antigens in the SCG. The two proteins studied were a 65 kilodalton integral membrane protein of synapatic vesicles (SV), and synapsin‐1 (S‐1), a synaptic vesicle phosphoprotein. Antigen levels were quantified by radioimmunoassay using antibodies directed against the proteins. Distribution of SV in control, deafferented and reinnervated ganglia from 30‐day‐old rats was visualized by immunohistochemical labeling. Levels of both antigens were reduced following deafferentation of the SCG on postnatal days 1–3. The reduction in S‐1 levels at 30 days was less than that observed for SV. The amount of S‐1 remaining in deafferented ganglia was consistent with estimates of the postsynaptic pool in the SCG reported previously. SV levels, in contrast, were reduced to 24% of control levels, suggesting that SV synthesis in principal ganglionic neurons might be affected. The time course of postnatal development of S‐1 in the SCG differed from previous studies of SV expression, with significant increases occurring after the second week after birth. The differences in response to deafferentation may reflect functional differences of the two vesicle‐associated proteins. These studies demonstrate that transsynaptic regulation of antigens other than those directly associated with neurotransmitters occurs in the SCG.
Physiological and morphological characterization of striatal neurons transplanted into the striatum of adult rats
Authors: Walsh John P. , Zhou Feng C. , Hull Chester D. , Fisher Robin S. , Levine Michael S. , Buchwald Nathaniel A.
Published: December 2004

Physiological and morphological properties of transplanted striatal neurons (TSNs) were examined in an in vitro slice preparation. Fetal striatal tissue (E13‐14) was implanted as a dissociated cellular suspension into the striatum of adult rats. Intracellular records were obtained from TSNs 2–6 weeks after transplantation. TSNs exhibited biophysical, morphological, and synaptic properties characteristic of normal striatal neurons, despite the disruption involved in processing of the fetal tissue. Differences were observed, however, between the TSNs and host striatal neurons. TSNs consistently had higher input resistance values than host striatal neurons as determined by neuronal responses to intracellular current injection. Stimulation of adjacent host striatum elicited both excitatory and inhibitory postsynaptic potentials in TSNs. By contrast, the same stimuli elicited only excitatory responses in host striatal neurons. Morphologically, TSNs resembled host medium‐size spiny neurons as demonstrated by intracellular injection of lucifer yellow. However, the complexity of dendritic branching and the density of spines on the dendrites were less than that observed for host striatal neurons. It was concluded that during the posttransplantation period studied, TSNs possess neuronal properties expected of developmentally immature striatal neurons.
Purification and characterization of PCPP‐260: A Purkinje cell‐enriched cyclic amp‐regulated membrane phosphoprotein of Mr 260,000
Authors: Weeks Gerald , Picciotto Marina , Nairn Angus C. , Walaas S. Ivar , Greengard Paul
Published: December 2004

PCPP‐260 (Purkinje cell phosphoprotein of Mr 260,000), a substrate for cAMP‐dependent protein kinase, appears to be an integral membrane protein highly enriched in Purkinje cells of the mammalian cerebellum (Walaas et al.: J. Neurosci., 3:291–301, 1983; Walaas et al.: J. Neurosci., 6:954–961, 1986). PCPP‐260 has now been purified from a crude particulate fraction of bovine cerebellum, using the ionic detergent N‐lauryl sarcosine (NLS) as solubilizing agent, and monitoring the purification by silver stain and autoradiography of 32P‐phosphorylated samples, after separation by sodium dodecyl sulfate‐polyacrylamide gel electrophoresis. Concanavalin A was found to bind to PCPP‐260, suggesting that it is a glycoprotein. PCPP‐260 was therefore extracted, retained on a column of concanavalin A‐agarose, and eluted by α‐methyl mannoside. Further chromatography on Sephacryl S‐400 yielded a preparation that was purified approximately 250‐fold relative to the initial particulate fraction and that was at least 95% pure. The protein was estimated to represent approximately 0.4% of total membrane protein in the cerebellum. Peptide mapping and phosphoamino acid analysis following phosphorylation of the protein by cAMP‐dependent protein kinase showed one major tryptic phosphopeptide containing phosphoserine. A similar, less prominent protein was also found in membranes from other brain regions but could not be detected in liver membranes. The availability of highly purified PCPP‐260 should facilitate the investigation of its possible functional roles in the nervous system.
Neurophysiological maturation of cat substantia nigra neurons: Evidence from in vitro studies
Authors: Walsh John P. , Cepeda Carlos , Buchwald Nathaniel A. , Levine Michael S.
Published: December 2004

The membrane properties and synaptic physiology of developing cat substantia nigra (SN) neurons were studied in in vitro slice preparations. Stable intracellular recording were obtained from 46 neurons in 20 kittens ranging in age from fetal day (F) 51 to postnatal day (P) 120. Only two of these properties changed with development. The percentage of cells displaying inward rectification and the percentage of cells that generated low‐threshold Ca++ spikes increased with age. Properties that did not change included resting membrane potentials, action potential amplitudes and durations, and input resistances. At all ages locally evoked synaptic responses consisted of sequences of excitatory postsynaptic potentials followed by inhibitory postsynaptic potentials. Most of the cells recorded had the electrophysiological properties which have been attributed to SN dopamine‐containing neurons. To identify neurons morphologically, and verify the recording site, cells were filled with Lucifer yellow at the end of each experiment. Somatic shapes varied widely from oval to fusiform to triangular. Somatic diameters and dendritic length increased with development. Filopodial processes and growth cones were present up to the first postnatal month. Dye‐coupling occurred only in the fetal group. These results indicate that cat SN neurons have many mature physiological properties during late fetal and early postnatal development. This contrasts with the significant maturation that occurs in cat caudate neurons during the same developmental period (Cepeda et al., Synapse, 7:278–290, 1991).
High affinity histamine binding site is the H3 receptor: Characterization and autoradiographic localization in rat brain
Authors: Cumming Paul , Shaw Christopher , Vincent Steven R.
Published: December 2004

The binding of the histamine autoreceptor (H3) agonist [3H]‐Nα‐methyl‐histamine ([3H]‐N‐MeHA) was examined in 25 μm thick rat forebrain sections. The specific binding was saturable and of high affinity: Scatchard analysis indicated a Kd of 2 nM and a Bmax of 25 ± 3 fmol/section. Under similar conditions, [3H]‐histamine ([3H]‐HA) bound with a Kd of 8 nM and a Bmax of 20 ± 2 fmol/section. Competition studies indicated that both ligands bound an identical site which had the pharmacological characteristics of the H3 binding site. The high affinity binding of [3H]‐N‐MeHA was sensitive to the presence of 5′ ‐guanylyl‐imidodiphosphate, indicating that the binding site is likely coupled to a G‐protein. Autoradiographic studies indicated the [3H]‐N‐MeHA binding to be greatest in the nucleus accumbens, striatum, substantia nigra pars reticulata, and certain cortical areas. Striatal quinolinic acid lesions greatly reduced binding in both the striatum and ipsilateral substantia nigra, while 6‐hydroxydopamine lesions of the nigrostriatal dopamine system were without effect on binding. Therefore, most of the H3 binding sites in the basal ganglia are on striatonigral projection neurons. Cortical quinolinic acid lesions greatly reduced H3 binding in cortex, indicating that the binding in cortex, as in striatum, is largely on intrinsic neurons, rather than on afferents such as histamine nerve terminals.
Morphological and electrophysiological study of distal motor nerve fiber degeneration and sprouting after irreversible cholinesterase inhibition
Authors: Kawabuchi Masaru , Cintra Wagner M. , Deshpande Sharad S. , Albuquerque Edson X.
Published: December 2004

A single subcutaneous injection of a sublelthal dose of the irreversible organophosphate sarin (0.08 mg/kg) in rat induced a non‐Wallerian‐type axonal degeneratin of the neuromuscular synapse in the slow twitch, soleus muscle. These alterations of the endplate region were more obvious in the soleus than in the fast extensor digitorum longus muscle and were slowly reversible, complete recovery requiring about 10 days. Silver‐cholinesterase staining and electrophysiological techniques were used to define the spatiotemporal evolution of prejunctional abnormalities. The non‐Wallerian‐type axonal degeneration of the neuromuscular synapse was characterized by bead or balloon‐like varicosities of the focal, dista, and terminal nerve fibers and a retraction of terminal axons. Axonal degeneration was accompanied by junctional and extrajunctional membran depolarization and was followed by nerve sprouting at focal, distal, and terminal nerve fibers. Transients similar to miniature endplate potentials were recorded along the muscle fiber at distances of 800–2500 μm away from the parent endplate. New ectopic endings, originating fromthe same endplate, were discovered adjacent to the terminal axon and also distant from the parent endplate. Very elaborate terminal arborization and occasional multibranching arose from a progressive growth sprout. The new sprouting may have served to compensate for the loss of synaptic contact caused by sarin. Thus the present study demonstrates a direct cytotoxic effect of sarin and indicates that this organophosphate agent may be an important neurotoxicological tool to understand the mechanisms involved in nerve sprouting.
[3H]1‐[2‐(2‐thienyl)cyclohexyl]piperidine labels two high‐affinity binding sites in human cortex: Further evidence for phencyclidine binding sites associated with the biogenic amine reuptake complex
Authors: Akunne Hyacinth C. , Reid Audrey A. , Thurkauf Andrew , Jacobson Arthur E. , de Costa Brain , Rice Kenner C. , Heyes Melvyn P. , Rothman Richard B.
Published: December 2004

Previous work demonstrated two high‐affinity PCP binding sites in guinea pig brain labeled by [3H]TCP (1‐{1‐[2‐thienyl]cyclohexyl}piperidine): site 1 {N‐methyl‐D‐aspartate [NMDA]‐associated} and site 2 {dopamine‐reuptake complex associated}. The present study examined brain membranes prepared from various species, including human, for the presence of site 2, defined as binding in the presence of (+)‐5‐methyl‐10, 11‐dihydro‐5H‐dibenzo[a,d]cyclohepten‐5, 10‐imine maleate ((+)‐MK801) minus binding in the presence of 10 μM TCP (nonspecific binding). Studies were conducted in absence of sodium which was found to be inhibitory to [3H]TCP binding. The results demonstrated detectable levels of site 2 in brain membranes of guinea pig, rabbit, pig, mouse, sheep, and human but not in the rat or chicken. Using human cortical membranes, site 2 was the predominant binding site. Detailed studies conducted with human cortical tissue showed that high‐affinity dopamine {1‐[2‐]bis(4[fluorophenyl)[methoxy]ethyl]4‐(3‐phenylpropyl)piperazine (GBR12909)}, [1, 2]benzo(b)thiophenylcyclo‐hexylpiperidine (BTCP), and serotonin (fluoxetine) uptake inhibitors produced a wash‐resistant inhibition of [3H]TCP binding to site 2, but not site 1. Preincubation of guinea pig brain membranes with BTCP was shown to produce an increase in the dissociation rate of [3H]TCP from PCP site 2. Structure activity studies with various uptake inhibitors showed that GBR12909, benztropine, fluoxetine, and BTCP have higher affinity for site 2 than for site 1. (+)‐MK801, ketamine, and tiletamine were very selective for site 1, whereas dexoxadrol and TCP were moderately selective for site 1. These results suggest that human cortex possesses high‐affinity PCP binding sites associated with biogenic reuptake binding sites, and that guinea pig brain, but not rat brain, may be an appropriate animal model for studying PCP site 2 in human brain.
Dopamine depletion produces augmented behavioral responses to a Mu‐, but not a delta‐opioid receptor agonist in the nucleus accumbens: Lack of a role for receptor upregulation
Authors: Churchill Lynn , Kalivas Peter W.
Published: December 2004

Microinjection of either m̈ ‐ or ð‐ opioid agonists into the nucleus accumbens produces an increased locomotor activity, and when the dopaminergic innervation of the nucleus accumbens is bilaterally lesioned, the locomotor response to the microinjection of mixed m̈‐ and ð‐opioid is augmented. To determine whether the lesion‐induced augmentation to opioids is specific to m̈‐ or ð‐ opioid receptor activation, dopamine innervation of the nucleus accumbens was lesioned with 6‐hydroxydopamine (6‐OHDA), and the motor stimulant response to intra‐accumbens microinjection of the selective m̈‐ opioid agonist, Tyr‐D‐Ala‐Gly‐mePhe‐Gly‐OH (DAMGO), was compared to that of the ð‐opioid agonist, [D‐penicillamine2.5]‐enkephalin (DPDPE). The lesions caused a 95% depletion of tissue dopamine levels in the nucleus accumbens of the DAMGO‐injected rats compared to sham‐lesioned rats. Horizontal and vertical photocell counts were significantly increased in response to DAMGO in 6‐OHDA‐lesioned compared to the sham‐lesioned rats. This behavioral augmentation was dose dependent and blocked by naloxone. In rats with similar accumbal dopamine depletions (94%), the locomotor response to DPDPE was not enhanced. The augmentation in the behavioral response to DAMGO was not associated with a change in the Bmax or Kd of [125I] DAMGO binding in nucleus accumbens homogenates form lesioned rats. Likewise, using quantitative receptor autoradiography, no difference between 6‐OHDA‐ and sham‐lesioned rats was observed in [125I]DAMGO or [125I]DPDPE binding. Therefore, the augmented behavioral response to opioids in the nucleus accumbens following dopamine depletion relies predominately on ð‐opioid receptor stimulation. However, this augmentation is not mediated by an alteration in the number or affinity of these receptors. © Wiley‐Liss, Inc.
Possible functions of a new genetic marker in central nervous system: The sulfated glycoprotein‐2 (SGP‐2)
Authors: Michel Denis , Chabot Jean‐Guy , Moyse Emmanuel , Danik Marc , Quirion Rémi
Published: December 2004

This brief review discusses the recent characterization in the brain of a gene coding for a protein that may be involved in programmed cell death and/or brain plasticity. We will term it sulfated glycoprotein‐2 (SGP‐2), the name corresponding to the first cDNA characterized. Recent studies have demonstrated the overexpression of this sulfated glycoprotein in various CNS disorders, such as certain gliomas, Alzheimer's disease and epilepsy, as well as after experimental brain injury in animals where different cell types were undergoing tissue remodelling or cell death. In peripheral tissues, SGP‐2 gene expression has been found to be strikingly increased following experimental manipulations in which cells of injured tissues were undergoing programmed cell death or apoptosis. The results reported thus far are intriguing and suggest the possible involvement of SGP‐2 in apoptotic mechanisms as well as its interaction with components of the immune system possibly associated with cell death in neurodegenerative disorders. © 1992 Wiley‐Liss, Inc.
Adenosine‐mediated synaptic inhibition: Partial blockade by barium does not prevent anti‐epileptiform activity
Authors: Birnstiel Susanne , Gerber Urs , Greene Robert W.
Published: December 2004

Adenosine‐induced inhibition of evoked postsynaptic potentials (PSPs) and epileptiform burst firing in the CA1 subfield of rat hippocampal slices was studied with intracellular recordings in vitro. Adenosine (50 μM) caused a membrane hyperpolarization which was abolished during superfusion with 2 mM Ba2+. The adenosine‐induced inhibition of the PSPs was still evident, although the magnitude of the effect was significanty reduced. Adenosine also reduced Ba2+‐induced burst firing, but less effectively than it did bursts evoked by TEA (5 mM). The results suggest that adenosine inhibits synaptic transmission and epileptiform activity by at least 2 mechanisms: a postsynaptic barium‐sensitive increase in gK and a presynaptic effect independent of this adenosine‐evoked outward potassium conductance. © Wiley‐Liss, Inc.
In vivo binding of [125I] RTI‐55 to dopamine transporters: Pharmacology and regional distribution with autoradiography
Authors: Cline Elizabeth J. , Scheffel Ursula , Boja John W. , Mitchell W. Mark , Carroll F. Ivy , Abraham P. , Lewin Anita H. , Kuhar Michael J.
Published: December 2004

Previous studies have demonstrated that para‐substituted WIN 35,065‐2 analogs of cocaine show high binding affinity for dopamine uptake sites both in vitro and in vivo, and inhibit DA uptake in vitro. These analogs also produce potent cocaine‐like behavioral effects in various procedures. The purpose of the present studies was to evaluate the iodinated WIN 35,065‐2 analog [125I] RTI‐55 as an in vivo ligand for the DA transporter. Following intravenous injection in mice, [125I] RTI‐55 showed highest accumulation in areas with high densities of dopamine uptake sites. Light microscopic autoradiography was used to examine binding with higher resolution. Displacement studies demonstrated that [125I] RTI‐55 binding in dopamine containing regions, striatum and olfactory tubercles, was saturable and inhibited by other cocaine analogs. GBR 12909 and WIN 35,428 significantly inhibited [125I] RTI‐55 binding in striatum, while paroxetine significantly inhibited hypothalamic binding but had little effect in striatum. The latter finding suggests that [125I] RTI‐55 also binds to the serotonin transporter. Haloperidol had no effect on [125I] RTI‐55 binding in any brain region measured. In addition, treatment of animals with the dopamine neurotoxin MPTP caused significant reductions in striatal [125I] RTI‐55 binding. The results of these studies indicate that [125I] RTI‐55 binds primarily to the dopamine transporter in the mouse striatum in vivo. Published 1992 Wiley‐Liss, Inc.
Biosynthesis of dopamine and serotonin in the rat brain after repeated cocaine injections: A microdissection mapping study
Authors: Baumann Michael H. , Raley Thomas J. , Partilla John S. , Rothman Richard B.
Published: December 2004

The purpose of the present study was to examine the effects of chronic cocaine on dopamine (DA) and serotonin (5‐HT) synthesis in several rat brain regions implicated in drug reinforcement. Male rats were treated twice daily with cocaine (15 mg/kg, ip) or saline for 1 week. After 42 hr of abstinence, rats were challenged with either cocaine (15 mg/kg, ip) or saline, followed by the aromatic L‐amino acid decarboxylase inhibitor 3‐hydroxybenzylhydrazine (NSD‐1015; 100 mg/kg, ip). Animals were decapitated 30 min after NSD‐1015 and discrete brain regions were microdissected from 300 μm frozen sections. Postmortem tissue levels of 3, 4‐dihydroxyphenylalanine (DOPA) and 5‐hyroxytryptophan (5‐HTP) were quantified by HPLC with electrochemical detection and used to estimate biosynthesis of DA and 5‐HT, respectively. In chronic saline‐treated rats, cocaine dramatically suppressed DA and 5‐HT synthesis in all forebrain regions examined, including: medial prefrontal cortex, nucleus accumbens, caudate nucleus, olfactory tubercle, and basolateral amygdala. The degree of inhibition ranged from 35‐65% and was more pronounced in 5‐HT neurons compared to DA neurons in the same tissue sample. In general, chronic cocaine did not significantly alter basal levels of DOPA or 5‐HTP; a notable exception was lateral hypothalamus, where chronic cocaine reduced basal DA synthesis to 75% of control. After repeated cocaine injections, the synthesisiinhibiting effect of a challenge injection of cocaine was attenuated in many brain areas. These data suggest that whereas acute cocaine decreases DA and 5‐HT synthesis in forebrain, chronic cocaine is not neurotoxic to DA and 5‐HT neurons. In addition, the mechanism(s) mediating cocaine‐induced suppression of monoamine synthesis may become desensitized by chronic exposure to the drug. Published 1993 Wiley‐Liss, Inc.
Hippocampal CRF, NE, and NMDA system interactions in memory processing in the rat
Authors: Lee E. H. Y. , Lee C. P. , Wang H. I. , Lin W. R.
Published: December 2004

In the present study, we investigated the neural mechanisms of corticotropin‐releasing factor (CRF) and the interactions among CRF, norepinephrine (NE), and N‐methyl‐D‐aspartate (NMDA) systems in the dentate gyrus (DG) of hippocampus in modulating the memory process of rats. One‐way passive avoidance task was adopted. Results indicated that CRF (80 ng), when directly injected into the DG, consistently and significantly enhanced memory retention in rats. The noradrenergic neurotoxin DSP‐4, at a high dose (4 μg), impaired memory. DSP‐4 at a moderate dose (2 μg), which did not affect retention alone, antagonized the memory‐enhancing effect of CRF. Similarly, the ß‐adrenergic antagonist propranolol, at a high dose (8 μg), reduced retention. At a low dose (80 ng), which did not markedly affect retention by itself, propranolol also prevented the memory‐improving effect of CRF. Moreover, direct NE infusions to the DG significantly improved retention performance in a dose‐sensitive manner. Coadministration of CRF and NE did not further enhance retention. These results together suggest that CRF and NE facilitated memory probably through the same instead of independent mechanisms. In contrast, the selective NMDA receptor antagonists 2‐amino‐5‐phosphonopentanoate (AP5) and MK801, at high doses markedly impaired memory retention (0. 8 and 3. 2 μg for AP5, 2 and 10 μg for MK801). At a dose of MK801 that did not significantly alter retention alone (80 ng), it completely blocked the memory‐facilitating effect of CRF. These results indicate that CRF enhanced memory indirectly through NMDA receptor mediation also. Finally, MK801 at 80 ng also successfully antagonized the memory‐facilitating effect of NE in the DG. We have demonstrated that MK801, at the dose chosen for interaction studies, did not markedly alter locomotor activity. These results together suggest that CRF, through a presynaptic facilitation mechanism, possibly facilitates NE release in the DG: increased NE release and stimulation of ß‐adrenergic receptors in the DG result in NMDA receptor activations in the same area. This sequence of events enhance the memory consolidation process in the hippocampus and explained the neural mechanism of CRF in facilitating retention performance in rats. The same neuropeptide/neurotransmitter interactions may have other physiological and neuropathological implications. © 1993 Wiley‐Liss, Inc.
Alterations in the dopaminergic receptor system after chronic administration of cocaine
Authors: Alburges Mario E. , Narang Neelam , Wamsley James K.
Published: December 2004

Several studies suggest that one of the most important factors contributing to cocaine dependence is an alteration in the actions of the neurotransmitter dopamine in the central nervous system. In order to understand some of the neuroreceptor consequences of cocaine administration, groups of rats were injected with cocaine (2 daily doses of 15 mg/kg) for 1 to 21 days. Binding of [3H]cocaine, [3H]SCH23390, [3H]raclopride, and [3H]BTCP in striatal and cortical tissue from the treated animals was compared to controls. [3H]Cocaine binding was increased by the drug in the striatum and cortex at days 14 and 21, respectively. The binding of [3H]SCH23390 to D1 dopamine receptors was significantly increased at day 3 of cocaine exposure. In striatal membranes, [3H]BTCP binding to dopamine uptake sites was significantly increased after day 7, whereas binding in cortical membranes was increased from day 1. [3H]Raclopride binding to D2 dopamine receptors remained unchanged throughout the study in both cortical and striatal tissues.

These results indicate that repeated exposure to cocaine produces an upregulation (possible supersensitivity) in cortical D1, cocaine, and DA‐uptake sites which occurs in a time‐dependent manner. These increases are coupled with an upregulation in striatal D1, cocaine, and DA‐uptake sites, without simultaneous changes in D2 receptors. Thus, cocaine's effects are not uniformly distributed across all brain regions, but rather are focused within areas of the dopamine system. © 1993 Wiley‐Liss, Inc.
Dopamine transporter mutants selectively enhance MPP+ transport
Authors: Kitayama Shigeo , Wang Jia‐Bei , Uhl George R.
Published: December 2004

MPP+ (1‐methyl‐4‐phenylpyridinium), a dopaminergic neurotoxin that provides the best available experimental model of Parkinson's disease, is selectively concentrated in dopamine neurons by the dopamine transporter (DAT). DAT also serves as a primary recognition site for cocaine. To help define selective molecular mechanisms by which MPP+ uptake occurs, we have tested dopamine transporters mutated in several residues for their abilities to accumulate dopamine and MPP+, and to bind a cocaine analog. Mutants in DAT 7th and 11th hydrophobic putative transmembrane domains increase MPP+ uptake velocity and affinity (1/KD), respectively. These mutations exert much more modest effects on dopamine uptake and have little impact on cocaine analog binding. These findings provide the first example of mutations that enhance transport and identify specific DAT amino acids selectively involved in neurotoxin uptake. They may also have implications for the feasibility of developing drugs that could specifically block accumulation of Parkinsonism‐inducing neurotoxins. © 1993 Wiley‐Liss, Inc.
Identification and characterization of striatal cell subtypes using in vivo intracellular recording in rats. I. Basic physiology and response to corticostriatal fiber stimulation
Authors: Onn Shao‐Pii , Berger Theodore W. , Grace Anthony A.
Published: December 2004

The electrophysiological characteristics of two subtypes of striatal neurons, identified by their distinct patterns of response to paired impulse stimulation of corticostriatal afferents, were compared using in vivo intracellular recordings in rats. As observed in previous extracellular recording studies, the majority of neurons (73%) were found to be of the Type II class, with the remaining cells exhibiting the Type I response patern. For all cells, cortical stimulation elicited 5–30 mV EPSPs at latencies ranging from 2.0–5.3 msec; Increasing the stimulating current intensity caused a progressive increase in the amplitude of the evoked EPSPs without altering their latencies, suggesting that the EPSPs are monosynaptically mediated. Both the average amplitude and duration of the evoked EPSPs at spike threshold in Type I neurons (9.8 ± 1.7 mV, 11.8 ± 2.8 msec; mean ± SEM) were significantly smaller than those of Type II cells (20.3 ± 1.4 mV, 22.7 ± 2.1 msec). Although the average latency to the onset of the EPSP was similar for both cell classes (Type I cells: 2.3 ± 0.3 msec; Type II cells: 2.2 ± 0.2 msec), the EPSPs in Type I cells reached peak amplitude and the spikes were triggered at significantly longer latencies than in the Type II cells (peak I: 11.2 ± 2.5 msec vs. II: 7.6 ± 0.7 msec; spike I: 8.0 ± 1.2 msec vs. II: 5.7 ± 0.4 msec).

Striatal neurons had a comparatively hyperpolarized resting membrane potential (−70.2 ± 2.1 mV) and had an average input resistance of 35.4 ± 7.6 MΩ. Overall, striatal neurons exhibited low levels of spontaneous activity (0.6 ± 0.7 Hz) with 50% of the neurons being quiescent. Type I cells exhibited significantly higher firing rates (3.2 ± 0.8 Hz) than Type II cells (0.8 ± 0.3 Hz), although their resting membrane potentials were not significantly different. Spontaneously occurring spikes had an average amplitude of 72.7 ± 3.4 mV and spike thresholds of −50.1 ± 1.5 mV. Irregularly occurring depolarizing plateau potentials, which typically gave rise to spike discharge, were frequently observed in both spontaneously firing and quiescent neurons. A small proportion of the cells recorded (3/55) exhibited a Type I response pattern but had unique physiological characteristics that were similar to those described by others as arising from large, aspiny striatal neurons.

The present study shows that these two physiologically distinct neuron types appear to be similar in terms of their passive membrane properties (e.g., resting membrane potentials, input resistance, etc.) and firing characteristics, despite their unique patterns of response to corticostriatal stimulation. Therefore, the source of the distinct paired impulse response profiles of these neurons is more likely to arise from differences in their afferent drive than from a heterogeneity in their membrane properties. © 1994 Wiley‐Liss, Inc.
Autoradiographic distribution of Mu opioid receptors in the brains of Cu/Zn‐superoxide dismutase mice
Authors: Kujirai Kayoko , Carlson Elaine , Epstein Charles J. , Cadet Jean Lud
Published: December 2004

Superoxide dismutase (SOD) is an important free radical scavenging enzyme which dismutates the superoxide anion radical. We have evaluated the role of SOD in the regulation of opioid receptors by comparing the concentration of μ opioid receptors labeled with [3H]DAGO (Tyr‐D‐Ala‐Gly‐NMe‐Phe‐Gly‐ol) in SOD‐transgenic (SOD‐Tg) mice and their non‐transgenic (Non‐Tg) littermates. SOD‐Tg mice had higher maximal binding capacity (Bmax) in the shell division of the nucleus accumbens (NAcshell) in comparison to Non‐Tg littermates. There were no differences in Bmax in μ receptors in the core subdivision of the nucleus accumbens (NAc‐core). There were no significant differences in receptor affinity (Kd) in either the NAc‐shell or in the NAc‐core. Moreover, there were no significant differences in either Bmax or Kd in the matrices nor in the patches of any of the striatal subdivisions. However, in a fashion similar to the situation in the NAc‐shell, [3H]DAGO binding in the substantia nigra pars compacta (SNpc), the ventral tegmental area (VTA), and the ventral part of the central grey was significantly higher in the SOD‐Tg mice in comparison to Non‐Tg mice. The present results are discussed in terms of their support for a possible involvement of free radicals in the differences observed in various regions of the SOD‐Tg and control mice, which differ in their ability to scavenge the superoxide anion. Moreover, because of the differences in β‐opioid receptors in the NAc‐shell, these transgenic mice might provide an excellent model in which to evaluate the role of the two accumbal subdivisions in paradigms of drug addiction, which appears to depend on the functional integrity of the mesocorticolimbic system. © 1994 Wiley‐Liss, Inc.

This article is a US Government work and, as such, is in the public domain in the United States of America.