bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dye‐Coupling in the neostriatum of the rat: I. Modulation by dopamine‐depleting lesions
Authors: Cepeda Carlos , Walsh John P. , Hull Chester D. , Howard Sherrel G. , Buchwald Nathaniel A. , Levine Michael S. 
Published: January 2005

AbstractEvidence from experiments performed in turtle and fish retina suggests that dopamine (DA) modulates the permeability of gap junctions. The present experiment was aimed at determining if DA has a similar role in the mammalian neostriatum. Adults rats received one of four treatments: Unilateral electrolytic substantia nigra lesions, unilateral injection of 6‐hydroxydopamine (6‐OHDA) into the substantia nigra, unilateral neocortical aspiration, or no treatment. After 3–5 weeks, neostriata from both sides of the brain were prepared for in vitro intracellular recordings. Recorded neurons (N α 150) were filled with Lucifer Yellow (LY), a low molecular weight dye that crosses gap junctions. In animals with electrolytic nigral lesions, dye‐coupling in the ipsilateral neostriatum occurred after 38% of the intracellular injections. After 6‐OHDA lesions, 19% of the injections produced dye‐coupling in the ipsilateral neostriatum. This difference may have been accounted for by the fact that electrolytic lesions produced a greater degree of DA loss than 6‐OHDA injections. Both of these percentages contrast with the very small percentage of dye‐coupling found in intact animals or in animals with neocortical lesions. Dye‐coupling occurred only between medium‐sized spiny cells. No morphological differences between dye‐coupled and non‐dye‐coupled cells were observed with light microscopy. Overall, passive and active electrophysiological properties of dye‐coupled and single neurons were similar. The results suggest that DA may function in the neostriatum to control permeability of gap junctions.
Presynaptic cholinergic inhibition in hippocampal cultures
Authors: Segal Menahem 
Published: January 2005

AbstractActivity of hippocampal neurons was recorded in a dissociated culture under patch‐clamp conditions. Excitatory and inhibitory postsynaptic currents (PSCs) were evoked in response to short pulse application of glutamate to other neurons in the culture dish. These PSCs were suppressed by topical application of acetylcholine (ACh) near the recorded neuron. The dose‐dependent effect of the muscarinic antagonist pirenzepine indicates that the effect of ACh is mediated by an M2 receptor. ACh did not affect inward current responses to direct application of glutamate onto postsynaptic neurons. This indicates that ACh may interfere with the release process and not with the postsynaptic response to the neurotransmitter. In some cells, ACh reduced inward Ca currents recorded in the presence of Na and K channel blockers. This effect was atropine sensitive and may underly the reduced PSCs. It is suggested that ACh modulates release of neurotransmitters by reducing presynaptic Ica and thereby reducing evoked PSCs.
Mapping cocaine binding sites in human and baboon brain in vivo
Authors: Fowler Joanna S. , Volkow Nora D. , Wolf Alfred P. , Dewey Stephen L. , Schlyer David J. , MacGregor Robert R. , Hitzemann Robert , Logan Jean , Bendriem Bernard , Gatley S. John , Christman David 
Published: January 2005

AbstractThe first direct measurements of cocaine binding in the brain of normal human volunteers and baboons have been made by using positron emission tomography (PET) and tracer doses of [N‐11C‐methyl]‐(–)‐cocaine ([11C]cocaine). Cocaine's binding and release from brain are rapid with the highest regional uptake of carbon‐11 occurring in the corpus striatum at 4–10 minutes after intravenous injection of labeled cocaine. This was followed by a clearance to half the peak value at about 25 minutes with the overall time course paralleling the previously documented time course of the euphoria experienced after intravenous cocaine administration. Blockade of the dopamine reuptake sites with nomifensine reduced the striatal but not the cerebellar uptake of [11C]cocaine in baboons indicating that cocaine binding is associated with the dopamine reuptake site in the corpus striatum. A comparison of labeled metabolites of cocaine in human and baboon plasma showed that while cocaine is rapidly metabolized in both species, the profile of labeled metabolites is different, with baboon plasma containing significant amounts of labeled carbon dioxide, and human plasma containing no significant labeled carbon dioxide. These studies demonstrate the feasibility of using [11C]cocaine and PET to map binding sites for cocaine in human brain, to monitor its kinetics, and to characterize its binding mechanism by using appropriate pharmacological challenges.
Coesxistence of corticotropin releasing factor and enkephalin in cerebellar afferent systems
Authors: Cummings Sharon , King James S. 
Published: January 2005

AbstractIn this study, we tested the hypothesis that corticotropin‐releasing factor (CRF) and enkephalin (ENK) coexist within restricted brainstem‐cerebellar circuits. Antisera for CRF and ENK were applied simultaneously or to serial sections of adult opossum brain and were processed for fluorescence or peroxidase, antiperoxidase immunohistochemistry, respectively. CRF and ENK were colocalized in (1) climbing fibers within the flocculus and in the cerebellar vermis; (2) fibers with morphological characteristics of simple mossy fiber terminals or climbing fiber glomeruli that were located within the granule cell layer of the vermis underlying the foci of CRF/ENK‐IR climbing fibers;(3) mossy fiber terminals within the flocculus; (4) neuronal perikarya in subnucleus A and C of the medial accessory olive and in the dorsal cap of Kooy, nuclei known to project as climbing fibers; and (5) cell bodies in nucleus propositus, the subtrigeminal reticular nucleus, and the reticular formation, likely origins of CRF/ENK colocalized mossy fibers. The demonstration that single climbing and mossy fibers contain two peptides extends previous studies that have described chemical heterogeneity within cerebellar afferent pathways. Furthermore, these results support suggestions that this heterogeneity may provide a substrate for differential regulation of signal transduction by chemically coded cerebellar afferents.
Vasopressin facilitates excitatory transmission in slices of the rat dorso‐lateral septum
Authors: Van Den Hooff Peter , Urban Ivan J. A. 
Published: January 2005

AbstractThe effects of vasopressin on neurons of the rat dorso‐lateral septum (DLS) was studied in brain slices with intracellular microelectrodes. Two out of 13 neurons showed a small depolarization, spontaneous activity, and increased input resistances following a 15 min exposure to 10‐6to 10‐8M vasopressin (VP). These membrane effects disappeared completely within 3–5 min after the application. The remaining DLS neurons treated with these vasopressin concentrations showed an increase in glutamate‐mediated excitatory postsynaptic potentials (EPSPs), evoked by stimulation of the fimbria fibers. As little as 10‐12M VP increase these EPSPsmarkedly in nearly 80% of the cells studied. This increase in most of the cells disappeared within 15 min after the application period, whereas the increase in EPSPsinduced by 10‐10M VP outlasted the peptide application period for more than 30 min. Neither the blockade of GABA‐ergic synaptic inhibition nor the pre‐treatment of the neurons with d(CH2)5‐Tyr(Me)‐arginine vasopressin or 2‐amino‐5‐phosphonovaleric acid (2‐APV), antagonists for the V1 type of vasopressin receptor and NMDA receptors, respectively, interfered with the EPSPspotentiating effect of the peptide. It is concluded that a type of vasopressin receptor other then the V1 type is involved in the long‐lasting potentiation of the primarily non‐NMDA receptor mediated transmission in DLS neurons.
Effects of high‐dose fenfluramine treatment on monoamine uptake sites in rat brain: Assessment using quantitative autoradiography
Authors: Appel Nathan M. , Mitchell Wm. Mark , Contrera Joseph F. , Desouza Errol B. 
Published: January 2005

AbstractFenfluramine is an amphetamine derivative that in humans is used primarily as an anorectic agent in the treatment of obesity. In rats, subchronic high‐dose d, l‐fenfluramine treatment (24 mg/kg subcutaneously, twice daily for 4 days) causes long‐lasting decreases in brain serotonin (5HT), its metabolite 5‐hydroxyindoleacetic acid, and high‐affinity 5HT uptake sites. Moreover, this high‐dose treatment regimen causes both selective long‐lasting decreases in fine‐caliber 5HT‐immunoreactive axons and appearance of other 5HT‐immunoreactive axons with morphology characteristic of degenerating axons. Determination of the potential neurotoxic effects of fenfluramine treatment using immunohistochemistry is limited from the perspectives that staining is difficult to quantify and that it relies on presence of the antigen (in this case 5HT), and the 5HT‐depleting effects of fenfluramine are well known. In the present study, we used quantitative in vitro autoradiography to assess, in detail, the density and regional distribution of [3H]paroxetine‐labeled 5HT and [3H]mazindol‐labeled catecholamine uptake sites in response to the high‐dose fenfluramine treatment described above. Because monoamine uptake sites are concentrated on monoamine‐containing nerve terminals, decreases in uptake site density would provide a quantitative assessment of potential neurotoxicity resulting from this fenfluramine ltreatment regimen. Marked decreases in densities of [3H]paroxetine‐labeled 5HT uptake sites occurred in brain regions in which fenfluramine treatment decreased the density of 5HT ‐like immunostaining when compared to saline‐treated control rats. These included cerebral cortex, caudated putamen, hippocampus, thalam us, land medial hypothalamus. Smaller, but nonetheless significant, decreases in density of [3H]paroxetine‐labeled 5HT uptake sites were noted in brain regions in which partial sparing of 5HT‐like immunoreactive fibers had been reported following fenfluramine treatment, specifically septum, lateral hypothalamus, and amygdala. In contrast, [3H]mazindol autoradiography revealed that total catecholamine (i.e., dopamine and norepinephrine) uptake sites in cerebral cortex, caudate putamen, and locus coeruleus, areas in which [3H]paroxetine‐labeled 5HT uptake sites were significantly decreased, were unaffecterd by this fenfluramine treatment. These data support the hypothesis that subchronic, high‐dose fenfluramine treatment causes selective degeneration of 5HT axons in rat brain. Since pharmacokinetic studies show that the dosing regimen used in this study exposes rat brain to concentrations of fenfluramine that are approximately 600 times greater than those resulting from the therapeutic oral dose, caution must be exercised in extrapolating these dat to humans.
Regulation of dopamine and serotonin synthesis by acute administration of cocaine
Authors: Galloway Mathhew P. 
Published: January 2005

AbstractBecause cacaine effectively increases extracellular levels of both dopamine (DA) and serotonin (5HT), it might be expected that this agent would inhibit transmitter biosynthesis in these monoamine neurons by activation of autoregulatory feedback pahwas. This possibility was tested by measuring the effect of cocaine on 3,4‐dihydroxyphenylalanine accumulation (DA synthesis) and 5‐hydroxytryptophan accmulation (5HT synthesis) in vivo and in vitro after inhibition of aromatic amino acid decarboxylase with NSD‐1015. In vivo, cocaine suppressed both Da and 5HT synthesis in a dose‐depentent (10–60 μmol/kg, i.p.) and time‐dependent fashion (maximum 60 min after administrationm, recovery by 120–150 min). Inhibition of Da and 5HT synthesis ranged from 35% to 60% depending on the brian region and was apparent in dopaminergic fields such as the medial prefrontal cortex, nucleus accumbens, piriform cortex, striatum, and in noradrenergic fields such as the hipocampus and temporal cortex. Inhibition of DA, but not 5HT, synthesis was blocked by the D2 antagonist sulpiride in brain areas containing DA nerve terminals. Procaine (30 μmol/kg) did not inhibit DA or 5HT synthesis and prior treatment with reserpine diminished the effectiveness of cocaine in the medial prefrontal cortex, but not in the striatum. Cocaine did not reverse the gamma‐butyrolactone‐induced increase in striatal DA synthesis nor did cocaine block the ability of the D2 agonist quinpirole to reverse the increase. In vitro, cocaine inhibited Da synthesis in depolarized (K+=30 mM) striatal brian slices, an effect that was reversed by the D2 antagonist eticlopride. These results suggest that DA and 5HT neurons compensate in situ for cocaine‐induced increases in synaptic transmitter levels by a transient inhibition of transmitter biosynthesis. Acute suppression of transmitter synthesis (and release) in mesoprefrontal DA neurcns may represent the principal compensatorty mechanism in this group of neurons.
Investigation of behavioral and electrophysiological responses induced by selective stimulation of CCKB receptors by using a new highly potent CCK analog, BC 264
Authors: Dauge V. , Bohme G. A. , Crawley J. N. , Durieux C. , Stutzmann J. M. , Feger J. , Blanchard J. C. , Roques B. P. 
Published: January 2005

AbstractThe new CCKB analog, Boc‐Tyr (SO3H)‐gNle‐mGly‐Trp‐(NMe)‐Nle‐Asp‐PheNH2(BC 264) exhibited a high affinity (KI = 0.39 ± 0.15 nM) and selectivity for central (B) versus peripheral (A) receptors (KI CCKA/KI CCKB = 910) in the rat. In agreement with these binding studies, BC 264 was at least 50 times more potent than CCK8 in stimulating the firing of rat CA hippocampal neurones. Furthermore sterotzxic injection of BC 264 or CCK8 in the VTA of rats resulted in potentiation of the dopamine‐induced hypolocomotion. These two types of CCK8 responses have been previously shown to involve CCKB receptrs. In contrast, after administration into the posteor‐median nucleus accumbens, the hypoexploration, the increase of emotionality of rats, or the potentiation of dopamine‐induced hyperlocomotion were obtained after injection of CCK8 but not of BC 264, supporting the involvement of peripheral CCKA receptors in these CCK8 responses. Owing to its resistance to peptidases, BC 264 appears to be of great interest in the investigation of the still uncertain funcitonal roles of CCK in the central nervous system.
Pharmacology of N‐methyl‐D‐aspartate‐induced brain injury in an in vivo perinatal rat model
Authors: McDonald John. W. , Johnston Michael V. 
Published: January 2005

AbstractIntrastratal injection of the glutamate analogue N‐methyl‐D‐aspartate (NMDA, 25 nmol) in postnatal (PND) 7 rats provides a rapid, sensitive, and reproducible assay in which potential neuroprotective strategies against excitotoxic neuronal injury can be examined in vivo. Brain injury is quantified 5 days postinjection by comparison of the weights of the injected and contralateral cerebral hemispheres. Intraperitoneal injections (15 minutes post‐NMDA) of competitive and noncometitive NMDA receptor antagonists attenuated the severity of NMDA‐induced brain injury. The rank order of neuroprotective potency of these antagonists was CGS‐19755<DOIPG<dextromethorphan<HA‐996. Of these compounds only the competitive antagonist CGS‐19755 provided complete neuroprotection. NMDA‐mdeiated brain injury was also reduced by the specific sigma receptor ligands + PPP and haloperidol (35% reduction). In contrast, drugs that reduce presynaptic neurotransmitter release (adenosine) or enhance neuronal inhibition (baclofen) were not effective against NMDA toxicity. Although all five of the anticonvulsants tested limited NMDA‐induced seizure activity, only carbamazepine reduced NMDA‐mediated brain injury (36% reduction). These findings extend earlier observations that NMDA receptor antagonists can limit NMDA‐induced toxicity in vivo and suggest that sigma receptors contribute to the pathophysiology of NMDA‐mediated brain injury in vivo. Furthermore, NMDA‐induced seizures and brain injury appear dissociable in this in vivo model. The results illustrate improtant practial limitations of neuroprotection in vivo vs.in vitro.
Autoradiographic localization of cocaine binding sites by [3H]CFT ([3H]WIN 35,428) in the monkey brain
Authors: Canfield Don R. , Spealman Roger D. , Kaufman Marc J. , Madras Bertha K. 
Published: January 2005

AbstractThe cocaine analog[3H]2β‐carbomethoxy‐3β‐(4‐fluorophenyl)tropane ([3H]CFT or [3H]WIN 35,428) binds with high affinity and selectivity to cocaine receptors in the monkey caudate‐putamen. [3H]CFT was used to map the regional distribution of cocaine binding sites in slide‐mounted sections of monkey brains using autoradiographic techniques. Hemicoronal brain sections were incubated with [3H]CFT (3 nM) alone or in the presence of excess (−)‐cocaine (30 μM) to mask the binding sites. High densities of [3H]CFT binding sites were detecte in the caudate nucleus, putamen, and nucleus accumbens. In all three regions, binding was markedly reduced by coincubatin with unlabeled (−)‐cocaine, indicating low levels of nonspecific binding. Little or no binding was observed in the cortex, thalamus, globus pallidus, or white matter tracts at the levels studied. In order to characterize biding sites for [3H]CFT in tissue sections, competition experiments were conducted using a fixed concentration of [3H]CFT (3 nM) and a range of concentrations of (−)‐cocaine, (+)‐cocaine, CFT, Lu 19‐005, GBR 12909, bupropion, and citalopram. The IC50 values for the drugs in tissue sections corresponded closely with their reproted IC50 values in monkey caudate‐putamen membranes (r =0.99, p <0.0001), suggesting that [3H]CFT binding is similar in the two preparations. These findings support the view that cocaine receptors labeled by [3H]CFT are localized predominantly in dopmaine‐rich brain regions implicated in the behavioral effects and abuse of cocaine.
Ultrastructural evidence of synaptic contacts between substance p‐, enkephalin‐, and serotonin‐immunoreative terminals and retrogradely labeled sympathetic preganglionic neurons in the Rat: A Study using a double‐peroxidase procedure
Authors: Vera Pedro L. , Holets Vicky R. , Miller Kenneth E. 
Published: January 2005

AbstractA double‐peroxidase procedure was used to study the ultrastructural relationship between terminals and fibers containing three putative neurotranasmitters and retrogradely identified sympathetic preganglionic neurons (SPNS) located in the intermediolateral cell column (IML) of the rat. SPNS with axons in the cervical sympathetic trunk were retrogradely labeled with horseradish peroxidase. In addition, terminals and fibers containing substance P, enkejphalin, and serotonin were detected using immunohistochemistry. Sections containing both retrogradely labeled SPNS and immunoreactive processes were processed for electron microscopy. Ultrastructural examination revealed synaptic contacts between terminals containing each of these three neurotransmitters and labeled dendrites from SPNS. Also, immunoreactive terminals were apposed to retrogradely labeled cell bodies. Therefore, these transmitters may alter sympathetic function by their direct action on SPNS.
Long‐Term synaptic potentiation in the amygdala
Authors: Chapman Paul F. , Kairiss Edward W. , Keenan Claude L. , Brown Thomas H. 
Published: January 2005

AbstractThe manner in which the circuitry of the amygdala computes its suspected mnemonic has been a mystery, partly cellular analysis. Here we report in vitro methods and results that may help elucidate cellular learning mechanisms in amygdala neurons. The amygdala brain slice preparation was combined with the single‐electrode clamp (sEC) technique for intracellular analysis of membrane properties and synaptic responses. With respect to the active and passive membrane properties, we found considered diversity among the population of cells that were sampled in the lateral and basolateral nuclei (n = 85). Synaptic inputs to these neurons were studied by stimulating the external capsule (EC), which was shown to produce a complex response that typically consisted of an excitatory followed by an inhibitory component. Based on serval criteria, the excitatory component apperred to reflect a monosynaptic connection from the EC. One immediate goal was to discover whether the excitatory component displays the phenomenon of long‐term potentiation (LTP)–a persistent increase in synaptic stimulation. Indeed, we found that high‐frequency (100 Hz) stimulation of the EC induced LTP in 80% of the cells from which suitable recordings were obtained (n= 20). This finding of LTP in the amygdala is significant in regard to current effort to explore linkages between this use‐dependent form of synaptic plasticity and rapid kinds of associative learning.
Long‐term potentiation of monosynaptic EPSPS in rat piroform cortex in vitro
Authors: Jung Min W. , Larson John , Lynch Gary 
Published: January 2005

AbstractInduction of long‐term potentiation (LTP) by burst stimulation patterned after the limbic system theta rhythm was studied in slices of piriform cortex. Monosynaptic responses were evoked by stimulation of afferent fibers of the lateral olfactory tract (LOT) or the intrinsic associational (ASSN) feedback system. LTP was difficult to elicit at LOT synapses in the presence of 2.5 mM extracellular Mg2+, and when it was induced potentiation increased for 20–30 min after burst stimulation before stabilizing. The probability of inducing LTP was increased when the extracellular Mg2+ concentration was reduced to 50μM. In ASSN system LTP developed in about 1 min after burst stimulation and then remained stable. ASSN system LTP was more readily induced in slices from caudal than rostral piriform. Induction of LTP at both LOT and ASSN synapses was blocked by D‐2‐amino‐5‐phosphonopentanoate, indicating that NMDA receptor activation was required. Neither system exhibited the decremental short‐term potentiation effect observed after burst stimulation of inputs to the CA1 field of hippocampus.
Age‐Related changes of strychnine‐insensitive glycine receptors in rat brain as studied by in vitro autroradiography
Authors: Miyoshi Rie , Kito Shozo , Doudou Naomi , Nomoto Teruko 
Published: January 2005

AbstractAge‐related changes of strychnine‐insensitive glycine receptors in the rat brain were studied through quantitative in vitro autoradiography with 3H‐glycine. 3H‐glycine binding sites were most concentrated in the hippocampus, cerebral cortex, and olfactory tubercle, and moderate densities of binding sites were located in the striatum, nucleus accumbens, amygdala, and certain thalamic nuclei. Low densities of 3H‐glycine binding sites were observed in the lateral septal nucleus, midbrain nuclei such as the superior colliculus and central gray matter, and granule cell layer of the cerebellum. In aged animals, severe decline of 3H‐glycine binding sites was observed in the telencephalic regions including the hippocampus and cerebral cortex. On the other hand, decrease of binding sites in the midbrain nuclei was of lesser degree, and there were no changes in the cerebellum. These results suggest that the decrease of glycine rceptors in particular brain regions has some reltion with changes of neuronal functions assocaited with aging process in these areas. The glutamatergic neuronal system, particularly the N‐methyl‐D‐aspartate (NMDA) subtype, has been considered to play an important role in learning and memory. Taking into consideration that strychnine‐insensitibve glycine receptors are contained in the NMDA receptor complex, the present study implies that the decrease of glycine receptors may be invloved in impairments of learning and memory occurring in aged brains.