bluuebunny/crossref_metadata_2025_split huggingface dataset:
“Strong” and “weak” synaptic differentiation in the crayfish opener muscle: Structural correlates
Authors: Govind C. K. , Pearce J. , Wojtowicz J. M. , Atwood H. L. 
Published: December 2004

AbstractThe single excitor motoneuron to the limb opener muscle in the crayfish Procambarus clarkii provides multiterminal innervation to individual muscle fibers. At low impulse frequencies, these neuromuscular synapses generate a threefold larger junctional potential in fibers of the proximal region of the muscle compared to those in the central region. Focal extracellular recording from synapse‐bearing “boutons” showed more quantal release at low frequencies in the proximal region. Structural correlates for the physiological differences were sought. Fluorescence microscopy of surface innervation stained with a vital fluorescent dye, 4‐Di‐2‐Asp, showed that density of innervation was not greater in the proximal region and thus could not account for the overall differences in synaptic strength. Freeze fracture studies showed that the intramembrane organization of excitatory synapses and their active zones was qualitatively similar in proximal and central sites. Serial section electron microscopy of several innervation sites in proximal and central regions showed homogeneity in number and size of synapses. However, presynaptic dense bars (at release sites, or active zones) were longer and occurred at a higher density in proximal than in central synapses. The differences in number and length of presynaptic dense bars correlate positively with the differences in synaptic strength represented by junctional potential amplitudes and quantal contents of individual surface recording sites. Since many individual proximal synapses have multiple dense bars, co‐operativity among these may serve to enhance transmitter output. It is concluded that occurrence of dense bars is a significant pre synaptic correlate of synaptic strength in this neuron. © 1994 Wiley‐Liss, Inc.
RTI‐4793‐14, a new ligand with high affinity and selectivity for the (+)‐MK801‐insensitive [3H]1‐[1‐(2 thienyl)cyclohexyl]piperidine binding site (PCP site 2) of guinea pig brain
Authors: Goodman Carl B. , Thomas D. Nigel , Pert Agu , Emilien Betsey , Cadet Jean L. , Carroll F. Ivy , Blough Bruce E. , Mascarella S. Wayne , Rogawski Michael A. , Subramaniam Swaminathan , Rothman Richard B. 
Published: December 2004

Abstract[3H]TCP, an analog of the dissociative anesthetic phencyclidine (PCP), binds with high affinity to two sites in guinea pig brain membranes, one that is MK‐801 sensitive and one that is not. The MK‐801‐sensitive site (PCP site 1) is associated with NMDA receptors, whereas the MK‐801‐insensitive site (PCP site 2) may be associated with biogenic amine transporters (BAT). Although several “BAT ligands” are known that bind selectively to PCP site 2 and not to PCP site 1 (such as indatraline), these compounds have low affinity for site 2 (Ki values > 1 μ). Here we demonstrate that the novel pyrrole RTI‐4793‐14 is a selective, high affinity ligand for PCP site 2. We determined the IC50 values of RTI‐4793‐14 and several reference compounds [PCP, (+)‐MK801 and indatraline] for PCP site 1 (assayed with [3H](+)‐MK801), PCP site 2 (assayed with [3H]TCP in the presence of 500 nM (+)‐MK801) and a variety of BAT‐related measures ([3H]CFT binding to the DA transporter, [3H]nisoxetine binding to the norepinephrine transporter, [3H]dopamine uptake, [3H]serotonin uptake). In addition, we determined the ability of RTI‐4793‐14 to block NMDA responses in cultured hippocampal neurons under voltage clamp. (+)‐MK801 had high affinity for PCP site 1 (4.6 nM) and potently inhibited NMDA‐induced responses, but was much less potent in the BAT‐related measures (IC50s > 10 μ). PCP had high affinity at PCP site 1 (IC50 = 92 nM) and PCP site 2 (IC50 = 117 nM), and was moderately potent in all BAT‐related measures except [3H]nisoxetine binding. Indatraline was potent in BAT‐related measures (IC50s, 2 to 5 nM), but weak in other measures (IC50s > 1 μ). In contrast, RTI‐4793‐14 had high affinity for PCP site 2 (38 nM), low affinity for PCP site 1 (> 36 μ), moderate IC50s for all BAT‐related measures, and negligible activity at NMDA receptors. Viewed collectively, these data indicate that RTI‐4793‐14 binds with high affinity and selectivity to PCP site 2 and provide further support for an association between PCP site 2 and the BATs. © 1994 Wiley‐Liss, Inc.
Activation of NMDA receptors in hippocampal area CA1 by low and high frequency orthodromic stimulation and their contribution to induction of long‐term potentiation
Authors: Grover Lawrence M. , Teyler Timothy J. 
Published: December 2004

AbstractN‐methyl‐D‐aspartate (NMDA) receptors are important in many instances of synaptic plasticity. In hippocampal area CA1, long‐term potentiation (LTP) can be induced by both NMDA receptor‐dependent and ‐independent mechanisms. Using intracellular recordings and single‐electrode voltage clamp, we isolated and characterized NMDA receptor‐mediated synaptic responses. NMDA receptor‐mediated responses evoked by low frequency orthodromic stimulation were inhibited in a dose‐dependent manner by the competitive antagonist D,L‐2‐amino‐5‐phosphonovaleric acid (APV). High frequency (tetanic) stimulation, which facilitates synaptic release of glutamate, failed to overcome the blockade of NMDA receptors by APV. Using extracellular recordings of field potentials, we studied the contribution of NMDA receptors to LTP induced by different patterns of tetanic stimulation. LTP was inhibited in a dose‐dependent manner by APV, but was more sensitive to APV than were NMDA receptor‐mediated synaptic responses. This most likely reflects a threshold for NMDA receptor activation in LTP induction. A component of LTP that resisted blockade by APV was induced by high (200 Hz), but not low (25 Hz), frequency tetanization. This NMDA receptor‐independent component of LTP persisted for > 4 hours and accounted for approximately half the potentiation induced by 200 Hz tetanization. Procedures necessary to induce LTP at the Schaffer collateral/ commissural synapses in area CA1 by both NMDA receptor‐dependent and ‐independent mechanisms are now well characterized. Using the same neuronal population, it will be possible to ask if processes involved in the maintenance of LTP are shared even when LTP is induced through two different mechanisms. © 1994 Wiley‐Liss, Inc.
Pet study of [11C] β‐CIT binding to monoamine transporters in the monkey and human brain
Authors: Farde Lars , Halldin Christer , Müller Lars , Suhara Tetsuya , Karlsson Per , Hall Håkan 
Published: December 2004

AbstractThe cocaine congener β‐CIT has been labeled with 11C for positron emission tomographic (PET) studies of the dopamine transporter. In the present autoradiographic study on human' brain sections and PET study on monkey and human [11C]β‐CIT accumulated markedly in the striatum. [11C]β‐CIT binding in the striatum was selective to the dopamine transporter. The binding in the thalamus was on an intermediate level and was displaced by compounds having affinity for norepinephrine and serotonin transporters. The neocortical binding was on a low level and could be displaced only by citalopram, a serotonin uptake inhibitor. A high dose of cocaine intravenously (7 mg/kg) induced a 50% occupancy of specific [11C]β‐CIT binding to the dopamine transporter in the striatum. This dose is much higher than the doses of 0.25‐0.5 mg/kg i.v. for cocaine arousal in human subjects. The finding indicates that cocaine arousal may be induced at a low dopamine transporter occupancy of a few percent. [11C]β‐CIT should be a useful radioligand to explore cocaine actions in humans and to follow the pathophysiological process in vivo by PET in neurodegenerative diseases of the striatum. © 1994 Wiley‐Liss, Inc.
Blockade of D‐1 dopamine receptors in the medial prefrontal cortex produces delayed effects on pre‐ and postsynaptic indices of dopamine function in the nucleus accumbens
Authors: Vezina Paul , Blanc Gérard , Glowinski Jacques , Tassin Jean‐Pol 
Published: December 2004

AbstractThe present experiments assessed the acute and delayed effects of D‐1 dopamine (DA) receptor blockade in the medial prefrontal cortex (mPFC) on pre‐ and postsynaptic indices of DA neurotransmission in the nucleus accumbens (N.Acc). Different groups of rats received intra‐mPFC injections of saline (control animals) or the D‐1 DA receptor antagonist SCH‐23390 (0.25 μg/side). Acutely, intra‐mPFC injections of this antagonist did not affect spontaneous locomotion but significantly increased the locomotion induced by intra‐N.Acc. amphetamine (1.5 μg /side), in agreement with our earlier findings [Vezina et al. (1991) Eur. J. Neurosci., 3:1001‐1007]. When tested two days post‐injection, however, mPFC‐SCH‐23390 preexposed animals showed lower levels of locomotor activity than Control animals in response to intra‐N.Acc. injections of amphetamine. This effect was not observed in other animals preexposed two days earlier to mPFC injections of amphetamine (2.5 tg/side) or the D‐2 DA receptor antagonist sulpiride (1.0 μg/side). Animals preexposed two days earlier to mPFC SCH‐23390 also showed higher levels of locomotor activity (+ 98%) when tested with intra‐N.Acc. injections of the D‐1 DA receptor agonist SKF‐38393 (1.0 μg/side) and a 36% increase in maximal DAsensitive adenylate cyclase activity in comparison to Control animals. These effects were no longer observed in animals tested seven days following the mPFC SCH‐23390 injections. These results demonstrate delayed actions resulting from cortical D‐1 DA receptor blockade. They suggest, in a way consistent with previous findings [Herve et al. (1989) J. Neurosci., 9:3699‐3708] that mPFC D‐1 DA receptors are involved in the presynaptic regulation of DA neuron reactivity as well as the postsynaptic regulation of D‐1 DA receptors in subcortical DA terminal and receptor fields such as the N.Acc. © 1994 Wiley‐Lies, Inc.
Buprenorphine and morphine produce equivalent increases in extracellular single unit activity of dopamine neurons in the ventral tegrnental area in vivo
Authors: Grant Steven J. , Sonti Gayatri 
Published: December 2004

AbstractBuprenorphine is a synthetic opioid proposed as a potential treatment for drug abuse. Although buprenorphine is widely considered to be a partial agonist at opioid receptors, little is known of its electrophysiological effects in the central nervous system. Because buprenorphine has been reported to have limited hedonic effects in humans, and since activation of the dopaminergic system is thought to be critical to the reinforcing effects of drugs, we compared the ability of buprenorphine and morphine to activate dopamine neurons. We report here that buprenorphine and morphine are equally effective in increasing the impulse flow of dopamine cells in the ventral tegmental area.Extracellular single unit activity was recorded from dopaminergic (DA) neurons in the ventral tegmental area (VTA) of chloral hydrate anethestized rats. Standard physiological and anatomical criteria were used to identify DA neurons. Systemic injection of buprenorphine (5–200 μg/kg, i.v.) and morphine (1–10 mg/kg, i.v.) produced equal magnitudes of activation in a similar subset of DA neurons in the VTA (buprenorphine: 173%; morphine: 164%). Unlike morphine, the activation by buprenorphine was not reversed by the opioid antagonist naloxone (50–100 μg/kg, i.v.), but this is consistent with the known pharmacodynamics of buprenorphine at opioid receptors.These studies demonstrate that acute administration of buprenorphine has morphinelike effects on the impulse activity of DA neurons. The implications for use of buprenorphine as a clinical treatment for drug abuse are discussed. © 1994 Wiley‐Liss, Inc.
Excitatory amino acid‐induced excitation of dopamine‐containing neurons in the rat substantia nigra: Modulation by kynurenic acid
Authors: Wu Hui‐Qiu , Schwarcz Robert , Shepard Paul D. 
Published: December 2004

AbstractKynurenic acid (KYNA), an endogenous antagónist of ionotropic excitatory amino acid (EAA) receptors, was tested for its ability to modulate N‐methyl‐D‐aspartate (NMDA)‐ and α‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionic acid (AMPA)induced excitation of dopamine (DA)‐containing neurons in the zona compacta of the rat substantia nigra (SNc). Experiments were conducted using extracellular recording techniques in conjunction with an in vitro brain slice preparation. Bath application of NMDA (1–20 μ) or AMPA (0.5–10 μ) produced a concentration‐dependent increase in the firing rate of SNc DA neurons but had no effect on firing pattern. The highest concentration of both agonists produced a rapid and reversible cessation of activity that was attributed to acute induction of depolarization block. Addition of glycino (GLY) (up to 100 μ) to the bathing solution had no effect on either basal firing rate or the increase in activity produced by NMDA. KYNA (10 μ–1 mM) antagonized the excitatory effects of both NMDA (15 μ) and AMPA (3 μ) in a concentration‐dependent fashion (IC50: 102 μ and 64 μ, respectively) without affecting basal firing rate. Perfusion of tissue slices with a modified Ringer's solution containing low Mg2+ (0.12 mM) increased NMDA‐induced excitation but did not affect the antagonist properties of KYNA. D‐serine (100 μ) reversed the ability of KYNA to block the excitatory effects of NMDA, suggesting that KYNA attenuates NMDA‐induced excitation of SNc DA neurons via blockade of the GLY allosteric site on the; NMDA receptor. The ability of KYNA to modulate the excitatory effects of both NMDA and non‐NMDA agonists implies that endogenous KYNA may play a physiological role it regulating DA cell excitability. © 1994 Wiley‐Liss, Inc.
Quantitative autoradiography of the serotonin transporter to assess the distribution of serotonergic projections from the dorsal raphe nucleus
Authors: Hensler Julie G. , Ferry Robert C. , Kovachich Gyula B. , Frazer Alan 
Published: December 2004

AbstractThe binding of 3H‐CN‐IMI to 5‐HT uptake sites, as measured by quantitative autoradiography, was used as a marker of serotonergic neurons. Within the dorsal raphe nucleus the binding of 3H‐CN‐IMI was compared in adjacent coronal sections of rat brain to the binding of 3H‐DPAT to 5‐HT1A receptors, which have a known somatodendritic localization. The heterogeneous pattern of binding of these two radioligands within the dorsal raphe nucleus was similar and corresponded to the distribution of serotonergic cell bodies as visualized by 5‐HT immunohistochemistry. Intracerebroventricular administration of 5,7‐dihydroxytryptamine (5,7‐DHT), which caused a dramatic loss of 5‐HT immunoreactivity and 3H‐DPAT binding to 5‐HT1A receptors, resulted in a marked reduction of 3H‐CN‐IMI binding in this nucleus. Treatment of rats with a dose of parachloroamphetamine (PCA) which has been reported to selectively lesion serotonergic processes arising from the dorsal raphe nucleus, while sparing serotonergic cell bodies and projections from the median raphe nucleus, did not alter the binding of 3H‐DPAT or 3H‐CN‐IMI in the dorsal raphe nucleus; serotonergic cell bodies appeared morphologically unaffected. The lack of effect of PCA treatment on the binding of 3H‐DPAT and 3H‐CN‐IMI is consistent with a somatodendritic localization of the 5‐HT transporter in the dorsal raphe nucleus. PCA treatment appeared to produce a moderate loss of serotonergic innervation in serotonergic terminal field areas as visualized by serotonin immunohistochemistry. The reductions in 3H‐CN‐IMI binding observed in terminal field areas (24 to 69%) following treatment of rats with PCA did not reflect a marked differential innervation of forebrain areas by the dorsal and medial raphe nuclei as expected from previous biochemical studies, and were not entirely consistent with the findings of neuroanatomical studies using histochemical techniques. Site‐specific injection of 5,7‐DHT into the dorsal raphe nucleus produced an 80 ± 11% reduction in the binding of 3H‐CN‐IMI in this nucleus, whereas the binding of 3H‐CN‐IMI in the median raphe nucleus was not reduced. The reductions in 3H‐CN‐IMI binding measured in the caudate putamen, frontal and entorhinal cortex as a result of specific lesion of the dorsal raphe nucleus were suggestive of a heavy innervation of these areas by the dorsal raphe nucleus as indicated in neuroanatomical studies. In the hippocampus, our data were consistent with an overlapping innervation of these areas by both the dorsal and median raphe nuclei and are not reflective of predominantt innervation by the medial raphe nucleus. © 1994 Wiley‐Liss, Inc.
Relationship between asymmetries in striatal dopamine release and the direction of amphetamine‐induced rotation during. The first week following a unilateral 6‐OHDA lesion of the substantia nigra
Authors: Robinson Terry E. , Noordhoorn Maura , Chan Emily M. , Mocsary Zoltan , Camp Dianne M. , Whishaw Ian Q. 
Published: December 2004

AbstractIn animals with a large unilateral 6‐hydroxydopamine (6‐OHDA) lesion of the nigrostriatal dopamine (DA) system the traditional “rotational behavior model” states that amphetamine will induce circling behavior towards the denervated striatum (ipsiversive), that is, away from the side where there is greater amphetamine‐stimulated DA release and greater DA receptor stimulation. It is puzzling, therefore, why amphetamine induces contraversive rotation in rats tested 4 days after a unilateral 6‐OHDA lesion, despite a 90‐95% loss of the dopaminergic input to the striatum by this time. Rats reverse their direction of amphetamine‐induced rotation by 8 days post‐lesion and turn in the ipsiversive direction thereafter. To try and resolve this paradox, bilateral striatal microdialysis was used to estimate the effects of amphetamine on DA neurotransmission on Day 4 and Day 8 following a large unilateral 6‐OHDA lesion of the substantia nigra. On Day 4 post‐lesion, amphetamine produced a moderate (around 50% of control) increase in the extracellular concentration of DA in the denervated striatum. This amphetamine‐releasable pool of DA was exhausted by a single amphetamine challenge, because a second injection of amphetamine given 3 h after the first did not produce a comparable increase in DA. It is suggested that on Day 4 post‐lesion the amount of DA released by amphetamine in the denervated striatum is sufficient to produce greater DA receptor stimulation on that side, because of DA receptor supersensitivity, and this leads to contraversive rotation. On Day 8 post‐lesion, amphetamine induced DA release in the intact striatum but had no effect on extracellular DA in the denervated striatum (DA was nondetectable). On Day 8, therefore, DA receptor stimulation would be greatest in the intact striatum, leading to ipsiversive rotation. In conclusion, it is suggested that the seemingly paradoxical reversal in the direction of amphetamine‐induced rotation that occurs over the first week following a unilateral 6‐OHDA lesion is consistent with the traditional rotational model, and is due to time‐dependent changes in the ability of amphetamine to release DA in the denervated striatum. © 1994 Wiley‐Liss, Inc.
The effects of chronic haloperidol administration on GABA‐immunoreactive. Axon terminals in rat medial prefrontal cortex
Authors: Vincent Stephen L. , Adamec Emil , Sorensen Ingrid , Benes Francine M. 
Published: December 2004

AbstractSeveral reports have suggested that chronic haloperidol (HAL) treatment induces ultrastructural changes in synapses of substantia nigra, corpus striatum, and medial prefrontal cortex (mPFC) of rat brain. The effects of HAL on specific cortical transmitter systems, however, are not well characterized. Recent studies have indicated that there may be a loss of gamma‐aminobutyric acid (GABA)ergic cells in anterior cingulate cortex of schizophrenic subjects and this hypothesis has prompted interest in the question of whether dopamine receptor antagonists, such as HAL, may influence the activity of this transmitter system. This current report describes a quantitative light microscopic analysis of GABA‐immunolabeled axosomatic terminals in mPFC of rats treated with HAL decanoate (0.5 mg/kg/day, i.m.) for a period of 4 months. GABA‐containing terminals were visualized with an avidin‐biotin immunoperoxidase method for localizing anti‐GABA antibodies. Computer‐assisted image processing was employed to determine the total number of pixels representing GABA‐immunoreaction product in axon terminals that were in direct apposition to pyramidal cell bodies. Drug‐treated animals showed a significant increase in the number of pixels representing GABA‐immunoreaction product in axosomatic terminals of layers II, III, V, and VI (93%, 63%, 31%, and 43%, respectively). These data are consistent with the idea that chronic HAL administration may be associated with a significant increase in the amount of GABA present in terminals surrounding pyramidal neurons of rat mPFC. The fact that GABA‐containing terminals showed the greatest increase in layer II is not consistent with the known distribution of dopamine afferents to this region which is lowest in superficial laminae. Based on the laminar distribution of non‐dopaminergic receptor types that have a high affinity for HAL, the effect of this drug on GABAergic transmission could potentially involve changes that are mediated through mechanisms in which 5‐HT2 or sigma opiate receptors play a role. © 1994 Wiley‐Liss, Inc.