bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alcohol inoxication does not change [11C]cocaine pharmacokinetics in human brain and heart
Authors: Fowler J. S. , Volkow N. D. , Logan J. , MacGregor R. R. , Wang G.‐J. , Wolf A. P. 
Published: December 2004

AbstractThere is increasing evidence that the combined use of cocaine and alcohokl produces enhanced behaviroal and toxic effects. We have used PET and tracer doses of [11C]cocaine in 7 normal human volunteers to assess if the dostribution and clearance of cocaine are altered by alcohlol intoxication. Each subject received 2 PET studies with [11C]cocaine (3–11 m̈g), one before and one during alcohol intoxication (1 g/kg). Regions of interest included dthe brain (n= 3) and heart (n = 4). arterial plasma was assayed for unchanged cocaine and for labelaed cocaethylene, a metabolite of cocaine found in individuals usig cocaine and alcohol in combination (hearn et al., 1991a). Alcohol intoxication did not change uptake and clearance or the steady‐state distribution volume of [11C]cocaine in brain (striatum, thalamus, and cerebellum) or in heart. Moreover, labeled cocaethylene was not detedted in the 10 minute plasma sample. These results suggest that the acute dnhancement of behavior and toxicity associated with the combined use of cocaine and alcohol is not due to an alteration in cocaine's organ distribution or to cocaethylene formation but may be related to an additive effect resulting from the direct actaons of each of these drugs. Published 1992 Wiley‐Liss, Inc.
In vivo studies of [125I]iodobenzamide and [11C]iodobenzamide: A ligand suitable for positron emission tomography and single photon emission tomography imaging of cerebral D2 dopamine receptors
Authors: Wong Dean F. , Wilson Alan A. , Chen Catherine , Minkin Elynne , Dannals Robert F. , Ravert Hayden T. , Sanchez‐Roa Patricia , Villemagne Victor , Wagner Henry N. 
Published: December 2004

AbstractIodobenzamide (IMB) labeled with either [11C] or [125I] was studied in mice and baboons. Pharmacological studies demonstrated an in vivo binding profile compatible with D2 dopamine receptors. Mouse biodistribution studies with both [11C]IMB and [125I]IMB showed a similar brain distribution of radioactivity. Mouse [125I]IMB studies with amphetamine and reserpine pretreatment suggested that IMB may be less susceptible to endogenous dopamine competition for D2 receptor binding in vivo as compared to raclopride. Preliminary baboon studies showed haloperidol competition for IMB binding sites. © 1992 Wiley‐Liss, Inc.
Fischer and Lewis rat strains differ in basal levels of neurofilament proteins and their regulation by chronic morphine in the mesolimbic dopamine system
Authors: Guitart Xavier , Beitner‐Johnson Dana , Marby David W. , Kosten Therese A. , Nestler Eric J. 
Published: December 2004

AbstractWe studied levels of neurofilament (NF) proteins in the ventral tegmental area (VTA), and other regions of the central nervous system, of two genetically inbred rat strains, Lewis (LEW) and Fischer (F344) rats. These strains represent genetically divergent populations of rats that have been used to study possible genetic factors involved in a variety of biological processes, including drug addiction: compared to F344 rats, LEW rats show a much higher preference for several classes of drugs of abuse. We found 30–50% lower levels of three NF proteins, NF‐200 (NF‐H), NF‐160 (NF‐M), and NF‐68 (NF‐L), in the VTA of LEW compared to F344 rats by use of immunolabeling and Coomassie blue staining. These strain differences were highly specific to this brain region, with no differences observed elsewhere in brain or spinal cord. Interestingly, chronic treatment of F344 rats with morphine decreased levels of these three NF proteins in the VTA, as found previously in outbred Sprague‐Dawley rats (Beitner‐Johnson, D., Guitart, X., and Nestler, E. J.: J. Neurosci., 12:2165–2176,1992), whereas morphine had no effect on NF levels in the VTA of LEW rats. A similar strain difference was observed in chronic morphine regulation of tyrosine hydroxylase, with morphine increasing enzyme immunoreactivity in the VTA of F344 rats (as has been observed previously in Sprague‐Dawley rats [Beitner‐Johnson, D., and Nestler, E. J.: J. Neurochem., 57:344–347, 1991]), but not in LEW rats. In view of the observations that LEW and F344 rats show different levels of preference for several types of drugs of abuse, and of the evidence supporting a central role of the mesolimbic dopamine system in drug reward mechanisms, the results of the current study suggest the possibility that levels of NFs and tyrosine hydroxylase may mediate some aspects of drug reinforcement and contribute to individual genetic differences in vulnerability to drug addiction. © 1992 Wiley‐Liss, Inc.
Role of the subthalamic nucleus in the regulation of nigral dopamine neuron activity
Authors: Smith Ian D. , Grace Anthony A. 
Published: December 2004

AbstractThe influence of subthalamic nucleus (STN) afferents on dopaminergic (DA) neurons of the rat substantia nigra (SN) was investigated. Hemisections of the brain placed between the STN and the SN or located anterior to the STN caused an increase in the firing rate of DA cells without producing significant changes in their firing pattern. In contrast, electrolytic and ibotenic acid lesions of the STN resulted in 93% and 49% reductions, respectively, in the level of burst firing without affecting the firing rate of DA cells recorded in the lateral SN. Furthermore, procedures which interrupted the STN input to the SN produced rapid pacemaker‐like firing in 18% of the lateral SN DA neurons recorded. Activation of the STN using single pulses of electrical stimulation caused: (1) a 20–50 msec inhibition of DA cell firing followed by an excitation, which in 35% of DA cells was accompanied by spikes occurring in a burst‐like pattern, and (2) a short‐latency inhibition lasting 5–25 msec in 75% of non‐DA SN zona reticulata (ZR) neurons. On the other hand, stimulation of the STN for 1 minute at 20 Hz resulted in an initial decrease in DA cell burst firing followed by elevated firing rates and increased burst firing by 30–60 minutes after the stimulation. Pharmacological activation of the STN by infusion of bicuculline caused a rapid inhibition of DA cells followed by a two‐fold increase in burst firing 6–14 minutes later, whereas SN ZR cells responded with an elevation in firing rate which dissipated in 6–14 minutes. Muscimol‐induced STN inhibition produced complimentary biphasic changes in SN neuron firing: (1) an initial increase followed by a decrease in burst firing and firing rate of DA neurons and (2) a rapid inhibition followed by an excitation of ZR cells over a similar time course. Thus, the STN appears to exert a dual action on SN DA cells: (1) initial inhibition possibly mediated through STN excitation of the inhibitory SN ZR projections to DA cells, and (2) a facilitation of burst firing which may be a direct effect of excitatory STN afferents. © 1992 Wiley‐Liss, Inc.
BMY‐14802, a sigma ligand and potential antipsychotic drug, reverses amphetamine‐induced changes in neostriatal single‐unit activity in freely moving rats
Authors: Wang Zhongrui , Haracz John L. , Rebec George V. 
Published: December 2004

AbstractThe effects of BMY‐14802 (5,10, or 20 mg/kg), a sigma‐receptor ligand showing preclinical evidence of antipsychotic efficacy, were tested on single‐unit activity in the neostriatum of freely moving rats with or without pretreatment with 1.0 mg/kg D‐amphetamine. Relative to resting baseline, amphetamine activated the large majority of neurons that changed firing rate in close temporal association with movement. All doses of BMY‐14802 reversed this neuronal response, but the effect was most pronounced at 20 mg/kg. This dose, however, was equally likely to reverse or to induce a haloperidol‐like potentiation of those neurons inhibited by amphetamine. In contrast, 10 mg/kg BMY‐14802 consistently reversed amphetamine‐induced neuronal inhibitions. All doses of BMY‐14802 attenuated the locomotor effects of amphetamine, but only the higher doses also blocked other aspects of the amphetamine behavioral response. By itself, BMY‐14802 dose dependently inhibited motor‐related neurons, but elicited less behavioral activation than amphetamine. BMY‐14802 (20 mg/kg) also induced hindlimb ataxia and occasional backwards locomotion. Haloperidol (1.0 mg/kg) reliably suppressed both behavior and neuronal activity when injected 30 min after BMY‐14802, whether or not amphetamine pretreatment was given. Thus, BMY‐14802 shares with other neuroleptics the capacity to reverse amphetamine‐induced excitations of neostriatal motor‐related neurons, whereas other effects of BMY‐14802 reveal some haloperidol‐like actions at 20 mg/kg that do not occur at lower doses. © 1992 Wiley‐Liss, Inc.
Glucose regulation of synaptic transmission in the dorsolateral septal nucleus of the rat
Authors: Shoji Shingo 
Published: December 2004

AbstractIntracellular recordings were made from neurons in the dorsolateral septal nucleus (DLSN) of rat brain slices. Lowering the concentration of extracellular glucose resulted in a concentration‐dependent membrane hyperpolarization associated with a cessation of spontaneous firing. The amplitude of the excitatory postsynaptic potential (EPSP), inhibitory postsynaptic potential (IPSP), and late hyperpolarizing potential (LHP) evoked by a single stimulus applied to the fimbrial/fornix pathway was decreased when the concentration of glucose was reduced to 0–2 mM. Substitution of glucose with 2‐deoxy‐D‐glucose (11 mM), and antimetabolite of glucose substrate, mimicked the effects of glucose depletion. Mannoheptulose (10–20 mM), a potent hexokinase blocker, and dinitrophenol (50 m̈M), a potent inhibitor of oxidative phosphorylation, produced both the hyperpolarization and inhibition of postsynaptic potentials, even in the presence of 11 mM glucose. The sulphonylureas, glibenclamide (10 m̈M) and tolbutamide (1 mM), did not antagonize the hyperpolarization and the inhibition of the postsynaptic potentials produced by glucose deplection. The amplitude of membrane depolarizations produced by pressure application of glutamate (10 mM) and the membrane hyperpolarizations produced by pressure application of either muscimol (1 mM) or baclofen (1 mM) were almost unchanged, even when glucose was reduced to 1–2 mM. These results indicate that intracellular glucose metabolism regulates the function of septal neurons, not only by changing the resting membrane potential, but also by presynaptically affecting neurotransmission between the hippocampal formation and the lateral septum. © 1992 Wiley‐Liss, Inc.
Effects of trifluoperazine on synaptically evoked potentials and membrane properties of CA1 pyramidal neurons of rat hippocampus in situ and in vitro
Authors: Agopyan N. , Krnjević K. 
Published: December 2004

AbstractThe effects of trifluoperazine (TFP), a phenothiazine antipsychotic, on hippocampal activity were studied in the CA1 subfield, both in situ and in slices. In the extracellular studies in situ and in vitro, both somatic population spikes and dendritic excitatory postsynaptic potentials (EPSP) fields were depressed reversibly by TFP, applied by microiontophoresis or in the bath (50‐100 μM). Similar effects were also seen during iontophoretic applications of sphingosine in situ. Like TFP (at micromolar concentrations) sphingosine is a dual Ca2+/calmodulin‐dependent kinase and protein kinase C (PKC) inhibitor. In intracellular recordings from slices, 50‐100 μM TFP induced a slow depolarization and a decrease in input resistance (RN), probably through a β‐aminobutyric acid (GABA)‐mediated increase in Cl− conductance (GCl). TFP also reduced the slow afterhyperpolarization (AHP) as well as electrically evoked inhibitory postsynaptic potentials (IPSPs), but EPSPs were augmented in both amplitude and duration. When CA1 neurons were voltage clamped, TFP elicited a corresponding inward current (consistent with depolarization), increased the leak conductance, and enhanced excitatory synaptic currents; whereas inhibitory synaptic currents and high‐threshold Ca2+ currents were reduced. In conclusion, these effects of TFP–which cannot be readily explained by its potent antidopamine action–are in keeping with other evidence that both Ca2+/calmodulin‐dependent kinase and PKC can modulate GCl‐conductance and high‐threshold Ca2+ ‐conductance, as well as inhibitory and excitatory postsynaptic currents. © 1993 Wiley‐Liss, Inc.
The cytochromes P‐450 are not involved in the modulation of the N‐methyl‐D‐aspartate response by sigma ligands in the rat CA3 dorsal hippocampus
Authors: Monnet Françlois P. , Debonnel Guy , de Montigny Claude 
Published: December 2004

AbstractRecent in vitro radioligand binding studies have shown that several cytochrome P‐450 inhibitors can displace [3H] sigma ligands, suggesting that these ligands might bind to the cytochrome P‐450 superfamily of enzymes. Using an in vivo electrophysiological model of extracellular recordings performed in the CA3 region of the rat dorsal hippocampus, we have previously shown that intravenous administration of low doses of several sigma ligands, such as 1, 3‐di(2‐tolyl) guanidine (DTG), JO‐1784, and (+)pentazocine potentiate the neuronal response induced by microiontophoretic applications of N‐methyl‐D‐aspartate (NMDA) without affecting those induced by quisqualate and kainate, suggesting that they act as sigma agonists. Conversely, the sigma ligands haloperidol, (+)3‐PPP, and BMY‐14802, which have no effect by themselves on the NMDA response, prevent and suppress the potentiating effect of sigma agonists on the NMDA response, suggesting that they act as sigma antagonists. The present studies were undertaken to determine if cytochromes P‐450 could be involved in the modulation of the NMDA response by sigma ligands. For this purpose, two cytochrome P‐450 inhibitors, proadifen (SKF‐525A) and piperonyl butoxide (PB), have been tested in our model.Unlike sigma agonists, at low doses, neither SKF‐525A nor PB affected the NMDA response of CA3 dorsal hippocampus pyramidal neurons. Unlike sigma antagonists, neither of these drugs reversed or prevented the DTG‐induced potentiation of the NMDA response. In addition, following high doses of SKF‐525A or PB, sufficient to induce a complete inactivation of cytochromes P‐450, DTG still potentiated the NMDA response.The present data suggest that cytochrome P‐450 inhibitors do not modulate the NMDA response like sigma agonists or antagonists do in this brain region. Furthermore, they rule out the involvement of cytochromes P‐450 in the modulation of the NMDA response by sigma ligands. © 1993 Wiley‐Liss, Inc.
Morphological and electrophysiological evidence for electrotonic coupling of rat dorsolateral septal nucleus neurons in vitro
Authors: Phelan Kevin D. , Twery Michael J. , Gallagher Joel P. 
Published: December 2004

AbstractIntracellular injections of Lucifer Yellow were utilized to evaluate the incidence of dye‐coupling among dorsolateral septal nucleus (DLSN) neurons recorded from slice preparations of adult rat septal nuclei. Twenty percent of single injections of Lucifer Yellow resulted in pairs of labeled neurons. These dye‐coupled cells were morphologically heterogeneous and did not exhibit any morphological characteristics that could be used to distinguish them from non dye‐coupled neurons. The spatial separation of cell bodies and close apposition of dendrites within each pair indicated that the dye transfer site(s) were situated at dendrodendritic and/or dendrosomatic rather than somatosomatic junctions. The main axon of some dye‐coupled neurons gave rise to intrinsic axon collaterals prior to exiting the nucleus indicating that these coupled neurons function as projection neurons as well as local circuit interneurons.Electrophysiological recordings of the passive membrane properties and spontaneous activity of individual dye‐coupled neurons revealed no significant difference from non dye‐coupled cells in the DLSN. Some neurons exhibited spontaneously occurring fast potentials which presumably represent electrotonic potentials. These fast potentials were often tightly coupled with action potentials but could be distinguished from synaptic potentials by their shape and their lack of voltage‐dependent changes in amplitude.These morphological and supportive electrophysiological data provide the first indirect evidence for electrotonic coupling of dorsolateral septal neurons. The functional significance of this coupling may lie in the potential for synchronization of the output of the DLSN which could play an important role in the septal maintenance and modulation of hippocampal Theta rhythm. © 1993 Wiley‐Liss, Inc.
Calcium‐dependent serine phosphorylation of synaptophysin
Authors: Rubenstein James L. , Greengard Paul , Czernik Andrew J. 
Published: December 2004

AbstractThe phosphorylation of synaptophysin, a major integral membrane protein of small synaptic vesicles, was found to be regulated in a Ca2+ ‐dependent manner in rat cerebrocortical slices, synaptosome preparations, and highly purified synaptic vesicles isolated from rat forebrain. K+‐induced depolarization of slices and synaptosomes prelabeled with 32P‐orthophosphate produced a rapid, transient increase in serine phosphorylation of synaptophysin. In synaptosomes, the depolarization‐dependent increase in synaptophysin phosphorylation required the presence of external Ca2+ in the incubation medium. The addition of Ca2+ plus calmodulin to purified synaptic vesicles resulted in a 4‐fold increase in serine phosphorylation of synaptophysin, and this phosphorylation was antagonized by a peptide inhibitor of Ca2+/calmodulin‐dependent protein kinase II (CaM kinase II). Purified rat forebrain CaM kinase II phosphorylated both purified synaptophysin and endogenous, vesicle‐associated synaptophysin, and the resulting 2‐dimensional chymotryptic phosphopeptide maps were similar to those derived from synaptophysin phosphorylated in cerebrocortical slices. These data demonstrate that Ca2+‐dependent phosphorylation of synaptophysin, mediated by CaM kinase II, occurs under physiological conditions. © 1993 Wiley‐Liss, Inc.
Long‐term potentiation in the avian hippocampus does not require activation of the N‐methyl‐D‐aspartate (NMDA) receptor
Authors: Wieraszko Andrzej , Ball Gregory F. 
Published: December 2004

AbstractEvoked potentials recorded from slices of pigeon hippocampus were reversibly attenuated by 2 mM kynurenic acid. High frequency stimulation (3 × 200 Hz for 1 sec, with 1 sec intervals) evoked a persistent increase in the evoked potential, lasting in a nondecremental form for at least 2 hr. This increase in the magnitude of the potential was not blocked by antagonists of the NMDA receptor (APV and MK‐801). These data suggest that the synaptic facilitation observed in the pigeon hippocampus, which appears to be a form of long‐term potentiation, does not depend on the activation of NMDA receptors. © 1993 Wiley‐Liss, Inc.
Beta‐adrenergic receptors in the hippocampal and retrohippocampal regions of rats and guinea pigs: Autoradiographic and immunohistochemical studies
Authors: Booze Rosemarie M. , Crisostomo Edgardo A. , Davis James N. 
Published: December 2004

AbstractSpecies differences in the distribution of β‐adrenergic receptors in the hippocampal and retrohippocampal regions of rats and guinea pigs were examined using in vitro autoradiographic techniques. β1‐receptors were found in the hippocampal area CA1 of both species, although guinea pigs had significantly lower receptor densities in comparison to rats. In guinea pigs, β2‐adrenergic receptors were predominant in hippocmpal area CA1. Hippocampal area CA3 had very low levels of β1‐ and β2‐receptors in both species. The retrohippocampal area was also found to have a distinct topographic distribution of β‐receptors. In rats, the subiculum and parasubiculum (layers II‐III) were heavily labeled for β1‐receptors; in contrast, guinea pigs had few receptors in these regions. β2‐receptors were particularly prominent in the parasubicular region in rats. The entorhinal cortex laminae was found to contain β‐receptors in both rats and guinea pigs. Immunohistochemical techniques were used to compare the pattern of catecholaminergic innervation with the receptor distribution within each hippocampal subregion. Despite the general lack of β‐receptors in area CA3, abundant catecholamine immunoreactive fibers were observed in CA3 of rat and guinea pig hippocampus. Significant species differences were found in the distribution of hippocampal β‐adrenergic receptor subtypes, and moreover, in both species the distribution of hippocampal β‐adrenergic receptors did not coincide with the pattern of hippocampal adrenergic innervation. © 1993 Wiley‐Liss, Inc.
Repeated administration of Sigma ligands alters the population activity of rat midbrain dopaminergic neurons
Authors: Zhang Jing , Chiodo Louis A. , Wettstein Joseph G. , Junien Jean‐Louis , Freeman Arthur S. 
Published: December 2004

AbstractAcute and repeated administration of antipsychotic drugs produce distinctive profiles of electrophysiological effects on the population activity of midbrain dopaminergic (DA) neurons which correlate with their clinical effects. Sigma receptors have been hypothesized to be involved in psychosis and in the efficacy of antipsychotic drugs, but little is known about the effects of repeated treatment with sigma ligands on the activity of midbrain DA neuronal populations. In the present study, the cells‐pertrack cell‐sampling method was used to evaluate the effects of 3 sigma ligands on the numbers of spontaneously active A9 and A10 DA neurons in chloral hydrate‐anesthetized rats. One‐hour pretreatment with either (+)‐pentazocine (10 mg/kg, i.p.), DTG (2 mg/kg, i.p.), or JO 1784 (1 or 10 mg/kg, s.c.) did not alter the number of spontaneously active DA neurons encountered per electrode track. Repeated treatment (21 daily injections) with (+)‐pentazocine (1 or 10 mg/kg) or DTG (0.2 or 2 mg/kg) increased the number of A10 DA cells per track; JO 1784 (10 mg/kg but not 1 mg/kg) moderately decreased the number of active A9 DA cells and increased the firing rate of A10 DA neurons. The effect of JO 1784 on A9 DA neurons was not due to depolarization inactivation. The effects of all 3 sigma ligands differ from those of antipsychotic drugs, all of which inactivate A10 DA neurons after repeated treatment. Clinical studies are necessary to determine if selective sigma ligands will provide a novel alternative to DA antagonists in the treatment of psychosis. © 1993 Wiley‐Liss, Inc.
In utero methamphetamine effects: I. Behavior and monoamine uptake sites in adult offspring
Authors: Weissman Arthur D. , Caldecott‐Hazard Sally 
Published: December 2004

AbstractChronic in utero methamphetamine treatment, throughout gestation in rats, resulted in alterations in both behavior and brain monoamine function in the adult offspring. The higher dose of methamphetamine (10 mg/kg/b.i.d.) caused a significant decrease in square crossing and rearing in an open field, as well as a region increase of serotonin and dopamine uptake sites. In contrast, the lower dose of in utero methamphetamine (2 mg/kg/b.i.d.) resulted in a significant decrease in regional densities of serotonin and dopamine uptake sites, and only decreased rearing behavior. Across treatment groups, there were significant correlations between open‐field square crossing activity and the number of uptake sites in specific brain areas. Other measured behaviors, such as the neonate righting reflex and the adult Morris water maze performance, were unaffected by either in utero drug regimen. These results are discussed in terms of the known neurotoxicity of amphetamines and the ability of the immature nervous system to compensate for fetal exposure to methamphetamine. © 1993 Wiley‐Liss, Inc.