bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pet studies of cocaine inhibition of myocardial norepinephrine uptake
Authors: Fowler Joanna S. , Ding Yu‐Shin , Volkow Nora D. , Martin Thomas , MacGregor Robert R. , Dewey Stephen , King Payton , Pappas Naomi , Alexoff David , Shea Colleen , Gatley S. John , Schlyer David J. , Wolf Alfred P. 
Published: December 2004

AbstractPositron emission tomography (PET), [11C]cocaine, and (–)‐6‐[18F]fluoronorepinephrine [(‐)‐6‐[18F]NE] were used to determine the extent to which the binding of labeled cocaine in the baboon heart represents binding to the norepinephrine transporter and to characterize the functional consequences of cocaine administration on the norepinephrine transporter. Peak heart binding of [11C] cocaine was high (0.038‐0.055%/g) and clearance was rapid (t1/2 from peak: 2.5–9 min) for both tracer doses and a pharmacological dose. The binding of a tracer dose of labeled cocaine could not be inhibited by desipramine, tomoxetine, cocaine, nomifensine, or benztropine. The behavior of a pharmacological dose of [11C]cocaine could not be distinguished from a tracer dose and also could not be inhibited by tomoxetine. However, pretreatment with cocaine profoundly inhibited norepinephrine uptake as assessed by (–)‐6‐[18F]NE. Recovery was slow with only 48% of the baseline (–)‐6‐[18F]NE uptake being recovered by 78 minutes after cocaine administration. [11C]Benzoylecgonine, a vasoactive metabolite of cocaine, showed negligible retention in heart. The results of this study (i.e., the rapid clearance of cocaine from the heart, the inability to inhibit cocaine binding with desipramine and tomoxetine, and its relatively long‐lasting effects on norepinephrine uptake) reinforce the need to understand the link between cocaine pharmacokinetics and norepinephrine transporter function and its relationship to cardiotoxicity. © 1994 Wiley‐Liss, Inc.
Receptor‐receptor link in membranes revealed by ligand competition: Example for dopamine D1 and D2 receptors
Authors: Seeman Philip , Sunahara Roger K. , Niznik Hyman B. 
Published: December 2004

AbstractAn interaction or link between dopamine D1 receptors and dopamine D2 receptors was found by a ligand competition method, using [3H]raclopride to label dopamine D2 receptors and SCH 23390 to block dopamine D1 receptors. In the presence of endogenous or exogenous dopamine, SCH 23390 increased the binding of [3H]raclopride in post‐mortem human striata homogenates or in tissue culture cells containing human dopamine D1 and D2 receptors. In order to reveal such intramembrane receptor‐receptor interactions in general, therefore, it appears essential to add two agonists, one for each receptor, and then to block one of the receptors when measuring the binding of a ligand to the second receptor. © 1994 Wiley‐Liss, Inc.
Muscarinic and nicotinic modulation of cortical acetylcholine release monitored by in vivo microdialysis in freely moving adult rats
Authors: Quirion Remi , Richard Jean , Wilson Amy 
Published: December 2004

AbstractThe aim of the present study was to investigate, using in vivo dialysis, the existence of muscarinic and nicotinic receptors controlling acetylcholine release in the cortex of freely behaving rats. Various muscarinic receptor antagonists, including the nonselective blocker atropine, and a variety of M2 drugs (AF‐DX 116, AF‐DX 384, AQ‐RA 741) potently stimulated, in a concentration‐dependent manner, the in vivo release of acetylcholine in the rat cortex. The effects of all these antagonists were long lasting. The nature of these putative muscarinic autoreceptors is likely of the pharmacologically defined M2subtype on the basis of the high potency of the antagonists of the AF‐DX series and the variability and shorter duration of action of the effects of the prototypic M1 blocker, pirenzepine. 4‐DAMP, a purported M3 blocker, also potently stimulated in vivo cortical acetylcholine release, but this likely relates to its now established, rather limited selectivity for any given muscarinic receptor subtypes. Peripheral and central injections of nicotine also induced the in vivo release of acetylcholine in the rat cortex, albeit with a lower potency and shorter duration of action than muscarinic antagonists. Interestingly, the combination of a muscarinic antagonist, such as atropine, AF‐DX 116, or AF‐DX 384, in the presence of nicotine, induced tremendous releases of cortical acetylcholine up to 8‐to 10‐fold over basal values. This is clearly more than a simply additive effect, and it reveals the great capacity of cortical cholinergic nerve terminals to synthesize and release acetylcholine. Optimal pharmacological manipulations of these putative muscarinic and nicotinic autoreceptors could thus be useful in disorders in which the activity of cholinergic inputs is decreased, such as in Alzheimer's disease. © 1994 Wiley‐Liss, Inc.
Brain uptake of α‐[14C]methyl‐para‐tyrosine in the rat
Authors: Cumming P. , Venkatachalam T. K. , Rajagopal S. , Diksic M. , Gjedde A. 
Published: December 2004

AbstractThe blood‐brain permeabilities of L‐[3H]tyrosine and the tyrosine hydroxylase (TH) inhibitor β‐[14C]methyl‐para‐tyrosine ([14C]AMPT) were determined in rat striatum, a brain region rich in TH activity, and in other brain regions containing relatively little TH activity. In striatum, the unidirectional clearance rate (K1) for L‐[3H]tyrosine (6.2 ml hg‐ −1 min−1) was significantly greater than the rates for L‐[14C]AMPT (2.8 ml hg−1 min−1) and D‐[14C]AMPT (0.8 ml hg−1 min−1). The apparent volume of distribution (Vf) for L‐[14C]AMPT in striatum (72.5 ± 4.0 ml hg‐1) did not differ from the Vf in other brain regions. The homogeneous distribution of L‐[14C]AMPT in rat brain indicates that labeled AMPT is unsuitable for the study of TH in vivo by quantitative autoradiography. © 1994 Wiley‐Liss, Inc.
Chronic ethanol exposure enhances [3H]GABA release and does not affect GABAA receptor mediated 36Cl uptake
Authors: Tremwel Margaret F. , Hunter Bruce E. , Peris Joanna 
Published: December 2004

AbstractChronic ethanol treatment (CET) produces a permanent reduction in hippocampal long‐term potentiation (LTP). The CET produced reduction of LTP can be eliminated acutely by Pharmacological blockade of γ‐aminobutyric acid (GABA)ergicA synaptic transmission with the specific antagonist, bicuculline methiodide. Since LTP induction is normally modulated by activation of GABAergic synaptic transmission, we hypothesized that CET reduced LTP by enhancing either postsynaptic GABAA channel function or GABA release from presynaptic terminals. In the present study, we examined the long term effects of CET on GABAA channel function by measuring the efficacy of GABA to stimulate and bicuculline to antagonize GABA‐stimulated 36Cl− uptake in hippocampal and cortical membrane preparations. CET did not affect basal uptake of chloride or the efficacy or either GABA or bicuculline at the GABAA channel. We next measured the long term effects of CET on basal and stimulated GABA release. When basal and electrically‐stimulated [3H]GABA release were measured in superfused hippocampal slices, stimulated release was increased by 30% in CET rats. Basal release was unaffected. Thus it appears that CET may be reducing LTP by enhancing plasticityrelated GABA release from presynaptic terminals. © 1994 Wiley‐Lisa, Inc.
Electrophysiological evidence for a functional interaction between 5‐HT1A and 5‐HT2A receptors in the rat medial prefrontal cortex: An lontophoretic study
Authors: Ashby Charles R. , Edwards Emmeline , Wang Rex Y. 
Published: December 2004

AbstractIn this study, we examined the interaction of 5‐HT1A and 5‐HT2A receptors in the rat medial prefrontal cortex (mPFc) using the techniques of extracellular single unit recording and microiontophoresis. The iontophoresis of the selective 5‐HT1A receptor agonist (±)‐8‐hydroxy‐2‐(di‐n‐propylamino) tetralin (8‐OHDPAT) produced a current‐dependent suppression (2.5‐20 nA) of the basal firing rate of spontaneously active mPFc cells. The iontophoretic (5‐10 nA) and systemic administration (0.1‐0.5 mg/kg, i.v. ) of the 5‐HT2A/5‐HT2C receptor antagonist ritanserin and the selective 5 HT2A receptor antagonist MDL 28727 significantly potentiated and prolonged 8‐OHDPATs suppressant action. In addition, the systemic administration of another selective 5‐HT2A antagonist MDL 100907, but not its less active enantiomer MDL 100009, also potentiated and prolonged 8‐OHDPATs action. The potentiating effect of the 5‐HT2A receptor antagonists on the action of 8‐OHDPAT is specific in that neither the iontophoresis of ritanserin nor MDL 28727 altered the suppressant action produced by the iontophoresis of the 5‐HT3 receptor agonist 2‐methylserotonin onto mPFc cells. Moreover, the suppressant action of 8‐OHDPAT was not altered by the systemic administration of the selective 5‐HT3 receptor antagonist granisetron (0.1‐0.5 mg/kg, i.v.). On the other hand, the iontophoresis of a low current (0.5 nA) of the 5‐HT2A,2C receptor agonist (±)‐1‐(2,5‐dimethoxy‐4‐iodophenyl)‐2‐aminopropane (DOI) potentiated the excitation induced by the iontophoresis of 1‐glutamate on quiescent mPFc cells. The iontophoresis of 8‐OHD‐PAT at a current that had no effect on the firing rate of 1‐glutamate activated when administered alone significantly attenuated the excitatory action produced by the iontophoresis of DOI. Overall these results confirm and extend the hypothesis that there is an interaction between 5‐HT1A and 5‐HT2A receptors in the mPFc at the neuronal level. © 1994 Wiley‐Liss, Inc.
Insulin‐like growth factor‐I receptors in human brain and pituitary gland: An autoradiographic study
Authors: De Keyser Jacques , Wilczak Nadine , De Backer Jean‐Paul , Herroelen Luc , Vauquelin G. 
Published: December 2004

AbstractInsulin‐like growth factor (IGF)‐I receptors were studied in adult human postmortem brain and pituitary gland using quantitative autoradiography with human recombinant [125I]IGF‐I. The highest densities were found in the choroid plexus, pituitary gland‐where IGF‐I receptors were mainly concentrated in the anterior lobe, pineal gland, glomerular layer of the olfactory bulb, and the molecular layer of the cerebellar cortex. Moderate densities were present in cerebral cortex, caudate nucleus, putamen, accumbens, the CA1, CA2, CA3 fields and dentate gyrus of the hippocampus, the dendate nucleus of the cerebellum, amygdala, thalamus, pontine nuclei, and substantia nigra. All other brain areas, including white matter, contained low densities of IGF‐I receptors. The finding that several well‐defined brain structures are enriched with IGF‐I receptors suggests a rieurotrophic/survival or neuromodulatory role of insulin‐like growth factors on specific neuronal systems. IGF‐I receptors observed in the white matter may be associated with oligodendrocytes. © 1994 Wiley‐Liss, Inc.
Methamphetamine‐induced neurotoxicity: Roles for glutamate and dopamine efflux
Authors: Stephans Stacy E. , Yamamoto Bryan K. 
Published: December 2004

AbstractThe neurotoxic effect of methamphetamine (METH) on striatal dopaminergic neurons have been hypothesized to be mediated by excess dopamine (DA) release. In addition, N‐methyl‐D‐aspartate (NMDA) receptor antagonists block METH‐induced DA depletions. This suggests that glutamate also mediates the toxic effects of METH. The purpose of this study is to demonstrate that DA and glutamate efflux contribute to METH‐inducted neurotoxicity.In vivo microdialysis in rats was used to measure extracellular concentrations of striatal DA and glutamate following 3 injections of METH (10 mg/kg, i.p.), each injection given 2 hours apart. One week following the dialysis experiment, rats were sacrificed and the ventral lateral striata were assayed for DA content. Glutamate concentrations in the dialysate increased by over 4‐fold after the third METH injection. In these same animals, striatal DA tissue content was significantly depleted. In separate groups of rats, pretreatment with haloperidol (2 mg/kg at the first METH injection) significantly increased METH‐induced DA efflux. The haloperidel pretreatment attenuated the extracellular increase in glutamate produced by METH and blocked subsequent neurotoxicity to DA neurons. In contrast, pretreatment with the DA uptake blocker, GBR‐12909 (10 mg/kg, 30 min before each METH injection) significantly attenuated the increased DA release produced by METH but did not change glutamate efflux. However, pretreatment with GBR‐12909 did protect against the tissue content depletion of DA in the striatum. Based on these findings, it appears that increased DA and glutamate release in the striatum are important and possibly interact in the development of METH‐induced neurotoxicity. © 1994 Wiley‐Liss, Inc.
Pharmacologically induced cessation of burst activity in nigral dopamine neurons: Significance for the terminal dopamine efflux
Authors: Nissbrandt Hans , Elverfors Anders , Engberg Goran 
Published: December 2004

AbstractResults obtained previously indicate that the firing pattern of midbrain dopamine (DA) neurons is of importance for the terminal DA release. In the present combined electrophysiological and microdialysis study, the influence of the firing pattern on striatal DA release was studied by using the previously observed ability of low doses of β‐hydroxybutyrate (GHBA) to profoundly regularise the firing pattern of rat DA neurons in the substantia nigra (SN). Administration of GHBA (200 mg/kg, i.v.) did not significantly reduce the firing rate of any of the DA neurons recorded from, but rather caused a slight transient excitation. However, this dose of the drug caused a profound regularisation of the firing pattern and abolished burst activity of the DA neurons. The DA concentration in the dialysate obtained from the striatum (10 min sampling periods) decreased with the lowest value (67% of predrug value) observed at the sampling period 20‐30 min after the GHBA administration. As a complement to microdialysis, the 3‐methoxytyramine (3‐MT) accumulation in striatal tissue following monoamine oxidase inhibition was determined as an indirect measure of DA release in vivo. The 3‐MT concentrations in the striatum decreased to 84% of controls following 200 mg/kg of GHBA. To exclude an effect on DA release conceivably mediated by GHBA locally in the striatum, GHBA (10−7‐10−3 M) was given locally in the dialysis probe and was found to increase DA in the dialysate (maximally to 140% of controls). The present results are in line with previous electrophysiological studies which have demonstrated that artificially induced burst firing by electrical stimulation is associated with an increased extracellular level of striatal DA (as determined by in vivo voltammetric techniques or microdialysis) and support the idea that firing pattern may be an important physiological modulatory mechanism for the release of terminal neurotransmitter. © 1994 Wiley‐Liss, Inc.
Insulin‐like growth factor binding protein‐1 at mouse neuromuscular synapses
Authors: Ma Jianxin , Yang Shi , Ho Gilbert J. , Festoff Barry W. 
Published: December 2004

AbstractThe insulin‐like growth factor (IGF) signaling system includes the growth factors and their cell surface receptors, along with circulating IGF binding proteins (IGFBPs) that may alter and modulate the action of these neurotrophic hormones. These IGFBPs, along with IGFs and receptors, have been detected in various tissues including the brain. In this study, using polyclonal antibody to human IGFBP‐1 or bovine IGFBP‐2, we found that mouse muscle extracts contain similar‐sized proteins that crossreact with these antibodies on Western immunoblots. After establishing that these antibodies reacted with the homologous murine IGFBPs, we performed immunocytochemistry to demonstrate the localization of IGFBP‐1 at the neuromuscular junction, a model nicotinic, cholinergic synapse, as well as within intramuscular nerves. IGFBP‐2, a distinct macromolecule, is present on the surface of muscle fibers and is not present within synapses or nerves. © 1994 Wiley‐Liss, Inc.
Dopamine neuron membrane physiology: Characterization of the transient outward current (IA) and demonstration of a common signal transduction pathway for IA and IK
Authors: Liu Lixin , Shen Roh‐Yu , Kapatos Gregory , Chiodo Louis A. 
Published: December 2004

AbstractDopamine neurons derived from the mesencephalon of embryonic rats were maintained in primary culture, identified and studied with whole‐cell patch recording techniques. These neurons demonstrated a rapidly activating and inactivating voltage‐dependent outward current which required the presence of K+ ions. This current was termed IA because of its transient nature. It was elicited by step depolarizations from holding potentials more negative than ‐50 mV and exhibited steady‐state inactivation at a membrane potential more positive than ‐40 mV and half‐maximal inactivation observed at ‐65 mV. This current rapidly achieved peak activation in less than 8 msec and decayed with a time constant (τ) of 58±5 msec. This current was observed in the presence of tetraethylammonium but was readily blocked by 4‐aminopyridine (2‐4 mM). This current was also observed to be modulated by stimulation of D2 dopamine receptors (DA autoreceptors) located on the dopamine neurons. Thus, both DA and the D2 receptor agonist quinpirole enhanced the peak IA observed, while the partial D1 receptor agonist SKF 38393 was without effect. The enhancement of IA was confirmed to be due to the activation of D2 receptors as the effects of either DA or quinpirole were blocked by the D2 receptor antagonists eticlopride and sulpiride, but not by the D1 receptor antagonist SCH 23390. Since we have previously demonstrated that the IK present: in these cells is also enhanced by D2 receptor stimulation, we investigated the signal transduction pathways involved in coupling DA autoreceptors to both IA and IK. The response of both these potassium currents to DA autoreceptor stimulation was completely abolished by the preincubation of cultures with pertussis toxin, indicating the possible involvement of the G proteins Gi and GO. In an attempt to further characterize which G protein may be involved, additional experiments were performed. The ability of DA autoreceptor stimulation to augment both currents was also blocked completely when G protein activation was prevented by the intracellular application of GDPßS (100 μM). In contrast, irreversible activation of G proteins by intracellular application of the nonhydrolyzable GTP analog GTPγS (100 μM) mimicked the effects of DA autoreceptor stimulation on both IA and IK. In addition, the intracellular application of a polyclonal antibody that was selective for the β‐subunit of GO completely abolished the DA autoreceptor modulation of both currents while preimmune serum was without effect. Taken together, these data demonstrate that the enhancement of IA and IK in response to stimulation of DA autoreceptors is dependent upon the activation of GO and appears to involve a GOα subunit. © 1994 Wiley‐Liss, Inc.
Calcium signalling in bovine adrenal chromaffin cells: Additive effects of histamine and nicotine
Authors: Firestone Jordan A. , Browning Michael D. 
Published: December 2004

AbstractIn a previous report, we described the ability of two secretogogues, histamine and nicotine, to stimulate additive effects on catecholamine (CA) release and synapsin II phosphorylation in bovine adrenal chromaffin cells (BACC) [Firestone and Browning (1992), J. Neurochem., 58:441–447]. We hypothesized that these results were due to the combined effects on cytosolic Ca++ of the two distinct signalling pathways. We therefore examined the intracellular Ca++ signals stimulated by histamine and nicotine, alone and together. In Ca++ ‐deficient medium, nicotine‐stimulated signals were abolished, whereas histamine‐stimulated signals were maintained, demonstrating that nicotine depended entirely on Ca++ influx for its effects. Indeed, the nicotine‐stimulated signal could also be prevented using a Ca++ channel blocker, nicardipine. Further, the observation that exposure of BACC to thapsigargin reduced histamine‐stimulated Ca++ signals verified that histamine mobilizes Ca++ from intracellular stores. Thus, the two secretogogues mobilize Ca++ from distinct pools. When BACC were stimulated with the two secretogogues together, the resulting Ca++ signal was greater than that from either alone. These data are consistent with a model in which two distinct sources of Ca++ can summate within the cell, producing a greater Ca++ signal and, hence, a greater effect on neurotransmitter release. © 1994 Wiley‐Liss, Inc.
Age‐dependent appearance of synaptic currents in rat neocortical neurons in culture
Authors: Zona Cristina , Palma Eleonora , Brancati Aldo , Avoli Massimo 
Published: December 2004

AbstractRat neocortical neurons grown in dissociated cell culture were recorded with the whole‐cell patch‐clamp technique. Spontaneous inward currents were observed in cells that were held at a membrane potential of −80 mV in medium containing tetrodotoxin and Cd2+. These currents displayed amplitudes up to 140 pA and rise time of 1.8 ± 0.2 ms (mean ± SD, n = 15). They reversed near 0 mV and showed no voltage‐dependent frequency of occurrence. Hence, they were presumably due to spontaneous release of transmitter. The inward currents appeared around day 10 in culture and were detected up to 4 weeks. When cells of different ages were compared, the maximal probability of recording these inward events occurred at around 3 weeks in culture. The inward currents were not reduced by application of bicuculline methiodide which is a competitive antagonist of the GABAA receptor, but were blocked by the broad‐spectrum glutamate receptor antagonist kynurenic acid. Moreover, spontaneous inward events were not affected by DL‐2‐aminophosphono‐valerate (NMDA receptor antagonist) but disappeared following application of the non‐NMDA receptors antagonist 6‐cyano‐7‐nitroquinoxaline‐2,3‐dione (CNQX). Our observations indicate that the inward currents represent miniature synaptic events that are primarily mediated by non‐NMDA excitatory amino acid receptor subtypes. Furthermore, our findings indicate that they develop over time and are not present in neurons that are grown in culture for less than 10 days. © 1994 Wiley‐Liss, Inc.
Immunohistochemical evidence for GABA and glycine‐containing trigeminal premotoneurons in the guinea pig
Authors: Turman Jack , Chandler Scott H. 
Published: December 2004

AbstractElectrophysiological studies have suggested that inhibition of trigeminal motoneurons during mastication and the jaw‐opening reflex are mediated by last‐order interneurons (premotoneurons) utilizing GABA and glycine [Chandler et al. (1985), Brain Res., 325:181–186; Enomoto et al. (1987), Neurosci. Res., 4:396–412; Goldberg and Nakamura (1968), Experientia, 24:371–373; Kidokoro et al. (1968), J. Neurophysiol., 31:695–708; Nakamura et al. (1978), Exp. Neurol., 61:1–14]. In the present study we performed a series of double‐labeling experiments in guinea pigs to determine the location of neurons which contain GABA (gamma aminobutyric acid) or glycine that project to the trigeminal motor nucleus (Mo5). This was accomplished by performing immunohistochemical staining in combination with a retrograde tract tracing technique using colloidal gold bound to inactivated WGA‐HRP (wheat germ agglutin‐horseradish peroxidase) (gWGA‐HRP) as our retrograde tracer. Neurons which had a positive immunoreactivity to GABA or GAD (glutamic acid decarboxylase) and contained the retrograde marker were located in regions adjacent to the Mo5 such as the intertrigeminal, supratrigeminal, peritrigeminal and rostral portions of the parvocellular reticular formation alpha. Neurons which had a positive immunoreactivity to glycine and contained the retrograde marker were identified in the parvocellular reticular formation, the spinal trigeminal nucleus oralis, supratrigeminal and intertrigeminal regions. These data provide anatomical evidence for GABAergic and glycinergic projections to Mo5. © 1994 Wiley‐Liss, Inc.