bluuebunny/crossref_metadata_2025_split huggingface dataset:
The novel N‐Methyl‐D‐Aspartate (NMDA) antagonist CGS 19755 prevents ischemia‐induced reductions of adenosine A1, NMDA, and PCP receptors in gerbil brain
Authors: Jarvis Michael F. , Murphy Deborah E. , Williams Michael , Gerhardt Susan C. , Boast Carl A. 
Published: January 2005

AbstractTransient brain ischemia results in a selective destruction of cell bodies within the hippocampus and cortex. This cellular destruction appears to be mediated through a release of endogenous exictatory amino acids following the ischemic episode, since the neurotoxic effects of ischemia can be attenuated by compounds that have antagonist activity at N‐methyl‐D‐aspartate (NMDA) receptors. In the present study, the protective effects of a novel NMDA receptor antagonist, CGS 19755, were further evaluated by using quantitative autoradiography to characterize adenosine A1, NMDA, PCP, and benzodiazepine receptors in ischemic gerbil brain. Bilateral carotid artery occlusion (20 minutes) resulted in marked decreases (30–60%) in adenosine A1, NMDA, and PCP, but not benzodiazepine, receptors in gerbil forebrain. Postischemic treatment with CGS 19755 was found to completely block the ischemia‐induced decreases in brain adenosine and NMDA receptors. [3H]TCP binding in ischemic gerbil brain was also elevated by CGS 19755 treatment; significant differences remained, however, between the CGS 19755‐treated and control gerbils. These results indicate that transient brain ischemia produces significant and selective alterations in gerbil forebrain receptor systems. The observed decreases in radioligand binding are probably reflective of an ischemia‐induced destruction of forebrain structures. However, there is some evidence that transient ischemia can also cause long‐term changes in the affinity of some receptor systems. The postischemic efficacy of CGS 19755 appears to be due to its ability to block the neurotoxic effects of transient ischemia.
Unilateral lesion of the nigrostriatal pathway decreases the firing rate and alters the firing pattern of globus pallidus neurons in the rat
Authors: Pan Helen S. , Walters Judith R. 
Published: January 2005

AbstractActivities of spontaneously firing neurons in the globus pallidus of intact rats and rats that survived unilateral lesions of the nigrostriatal pathway for 3 days, 1 week, or 6–11 weeks were compared. No significant differences in neuronal firing rate, firing pattern, and number of cells per pass were observed between chloral hydrate‐anesthetized control and lesioned animals. However, in locally anesthetized animals, pallidal cells fired significantly faster than in chloral hydrate‐anesthetized animals, and the lesion caused a decrease in the firing rates of pallidal cells 1 week and 6–9 weeks postlesion. In addition, significant differences in the firing pattern of pallidal cells, as determined by the ratio of the mean to median interspike intervals, were seen between locally anesthetized controls and animals surviving 3 days, 1 week, and 6–9 weeks post lesion. This altered firing pattern tended to return to normal with time. The number of cells per pass was not significantly altered by the lesion. Data from this study suggest that, in locally anesthetized animals, the removal of the tonic dopaminergic input to the basal ganglia causes pallidal cells to decrease their firing rates in a time‐dependent fashion and causes reversable firing pattern changes. This suggests that tonically active dopamine neurons, probably acting through the striatopallidal pathway, regulate the firing rate and mechanisms controlling the temporal ordering of spontaneous discharges of globus pallidus neurons.
Properties of two classes of rat brain acidic amino acid receptors induced by distinct mRNA populations in Xenopus oocytes
Authors: Fong Tung Ming , Davidson Norman , Lester Henry A. 
Published: January 2005

AbstractThe Xenopus laevis oocyte expression system was used to study the molecular composition of mRNAs encoding acidic amino acid (AA) receptors from rat brain. Xenopus oocytes injected with poly(A) mRNA express two general classes of AA receptors. One class consists of AA‐gated cation channels. Responses are evoked by N‐methyl‐D‐aspartate (NMDA), by kainate, and to a lesser extent by L‐glutamate or quisqualate. The second class of receptor is coupled to an intracellular second messenger pathway activating an oocyte‐encoded Ca2+‐activated Cl− conductance. This second messenger‐coupled AA receptor can be activated by L‐glutamate or quisqualate. DL‐2‐amino‐5‐phosphonopentanoic acid and D‐α‐aminohexanedioic acid inhibit the AA‐gated cation conductances activated by NMDA or kainate with different potencies but do not inhibit the second messenger‐coupled AA receptor. Responses to NMDA are enhanced by micromolar level of glycine and are inhibited by Mg2+, Zn2+, or MK‐801. Dose‐response analysis reveals that the AA‐gated cation conductance activated by kainate requires the binding of two agonist molecules. To study the molecular composition, the mRNAs were size fractionated by denaturing agarose gel electrophoresis. About20‐fold purification in specific activity (nA/ng of mRNA injected) of mRNAs encoding the second messenger coupled AA receptor was achieved. In contrast, only a slight enrichment of the mRNAs encoding the AA‐gated channel was observed. This suggests that the second messenger coupled AA receptor is encoded by a single size class of mRNA, whereas the AA‐gated cation channel(s) is encoded by multiple species of mRNAs or by mRNAs whose size distribution is heterogeneous.
Effects of nicotinic agonists and antagonists on N‐methyl‐D‐aspartate‐induced 3H‐norepinephrine release and 3H‐(1‐[1‐(2‐thienyl)cyclohexyl]‐piperidine) binding in rat hippocampus
Authors: Snell Lawrence D. , Johnson Kenneth M. 
Published: January 2005

AbstractThe nicotinic agonists dimethylphenylpiperazinium iodide (DMPP) and carbachol (CARB) as well as (−)nicotine ((−)NIC) were tested alone and in combination with N‐methyl‐D‐aspartate (NMDA) for their abilities to enhance the efflux of 3H‐norepinephrine (NE) from slices of rat hippocampus. CARB and (−)NIC produced small, transient increases in NE efflux, while DMPP produced larger, longlasting increases. Inasmuch as the nicotinic antagonists mecamylamine (MECA) and hexamethonium (C6) did not consistently inhibit the increases in NE efflux produced by these agonists, the role of a nicotinic receptor in mediating these responses is uncertain. CARB and DMPP enhanced the ability of NMDA to stimulate NE release, while (−)NIC did not. MECA, but not C6, was found to selectively antagonize NMDA‐stimulated NE release that did not appear to involve a nicotinic receptor. Binding studies indicated that MECA and the related nicotinic antagonist pempidine produced an inhibition of NMDA‐stimulated NE release by an action at the PCP receptor that is known to be linked to the NMDA receptor‐ionophore complex. These data suggest that the actions of these ganglionic blocking agents on excitatory responses in the hippocampus involve inhibition of excitatory amino acid as well as nicotinic receptors.
Classical conditioning in rabbits using pontine nucleus stimulation as a conditioned stimulus and inferior olive stimulation as an unconditioned stimulus
Authors: Steinmetz Joseph E. , Lavond David G. , Thompson Richard F. 
Published: January 2005

AbstractClassical conditioning of skeletal muscle responses was accomplished by pairing microstimulation of the pontine nuclei as a conditioned stimulus (CS) with microstimulation of the dorsal accessory olive as an unconditioned stimulus (US). A conditioned response identical in form to the behavioral response elicited by the olivary stimulation was established when the CS was forward paired with the US, and behavioral extinction occurred with CS‐alone presentations or unpaired CS‐US presentations. Conditioned responding could not be established or maintained when the CS and US were simultaneously presented or when the US preceded the CS (i.e., backward paired). Complete lesions of the interpositus nucleus abolished both conditioned and unconditioned responses. These findings support the idea that plasticity associated with classical conditioning of skeletal muscle responses occurs in regions of the cerebellum that receive convergent CS and US input.
Detection and characterization of a 5HT1D serotonin receptor‐gtp binding protein interaction in porcine and bovine brain
Authors: Herrick‐Davis Katharine , Titeler Milt 
Published: January 2005

AbstractRadioligand binding studies were performed to characterize serotonin 5HT1D binding sites in porcine and bovine brain. 3H‐5HT binding, in the presence of 1 μM (+/−)pindolol (to block 5HT1A and 5HT1B receptors) and 100 nM mesulergine (to block 5HT1c receptors), was specific, saturable, and of high affinity. In porcine and bovine cortex and striatum the majority of 5HT1 sites (80%‐90%) were of the 5HT1D subtype. In competition experiments 8‐OH‐DPAT, TFMPP, mesulergine, DOB, and ICS 205‐930 had low affinity for 3H‐5HT‐labeled 5HT1D sites, indicating that the pharmacology of the 5HT1D site is distinct from previously identified 5HT1A, 5HT1B, 5HT1C, 5HT2, and 5HT3 sites. Guanyl nucleotides, GTPgammaS, and Gpp(NH)p, and divalent cations potently modulated the binding of 3H‐5HT to 5HT1D sites in porcine and bovine striatum. Mg+ + ions increased the number and affinity of 3H‐5HT‐labeled 5HT1D sites, while guanyl nucleotides decreased the number of 3H‐5HT‐labeled 5HT1D sites. These results demonstrate the presence of the 5HT1D receptors in porcine striatum and bovine cortex and provide direct demonstration that the radioligand binding assay for the 5HT1D receptor can monitor the interaction of this receptor with a GTP‐binding protein.
Intracellular studies in the facial nucleus illustrating a simple new method for obtaining viable motoneurons in adult rat brain slices
Authors: Aghajanian George K. , Rasmussen Kurt 
Published: January 2005

AbstractIn general, it has been difficult to preserve electrophysiologically viable motoneurons in brain slices from adult mammals. The present study describes a new method for obtaining viable motoneurons in the facial nucleus of adult rat brain slices. The essence of the method was to use a modified artificial cerebrospinal fluid (ACSF) in which NaCl was replaced initially by sucrose; the modified ACSF was used during (1) slice preparation and (2) a 1 hr recovery period. The rationale for the modification is discussed in terms of the proposed acute neurotoxic effects of passive chloride entry and subsequent cell swelling and lysis. The actual recordings were made only after switching back to normal ACSF. Use of this method yielded large numbers of viable motoneurons that were suitable for intracellular recording; no motoneurons survived when normal ACSF (i.e., with NaCl) was used during slice preparation. A survey of some electrophysiological and pharmacological properties of facial motoneurons in this preparation, by means of current‐clamp and voltage‐clamp recording, revealed close similarities to the properties of adult motoneurons previously observed in vivo (e.g., time‐dependent inward rectification, apamin‐sensitive afterhyperpolarization, and serotonin‐induced slow depolarization).
Alterations in local cerebral glucose utilization following central administration of corticotropin‐releaseing factor in rats
Authors: Sharkey John , Appel Nathan M. , De Souza Errol B. 
Published: January 2005

AbstractWe have examined the effects of intracerebroventricular administration of corticotropin‐releasing factor (CRF) (5.25 nmol in 10 μl of saline) on glucose utilization, an index of cerebral function, in 65 anatomically discrete regions of rat brain by using the 14C‐2‐deoxyglucose quantitative autoradiographic technique. CRF administration increased plasma glucose concentrations with a temporal onset and magnitude of response similar to those previously reported. CRF differentially affected glucose utilization (GU) in discrete regions of rat brain. Consonant with the hypophysiotropic role for CRF, pronounced increases in GU were seen in median eminence and lateral nucleus of the hypothalamus. CRF also increased GU in brain regions implicated in mediating responses to stress including locus coeruleus and median raphe nucleus. In contrast, reductions in GU were observed in prefrontal cortex and nucleus accumbens. Punctate increases in GU were noted in the cerebellar cortex. Furthermore, large increases in GU occurred in vermis, inferior olive, and red nucleus substantiating a neurotransmitter role for CRF in the olivocerebellar pathway. Additional brain areas showing significant alterations in GU in response to CRF included anteroventral, anterior pretectal, and posterolateral nuclei of the thalamus, fornix, dorsal tegmental nucleus, spinal trigeminal nucleus, and cuneate nucleus. These data demonstrating regional changes in GU in response to CRF administration further elucidate the neuroanatomical substrates underlying the actions of CRF in brain and support the role of this neuropeptide in coordinating responses to stress.
Associative synaptic potentiation and depression: Quantification of dissociable modifications in the hippocampal dentate gyrus favors a particular class of synaptic modification equations
Authors: Lopez Hector S. , Burger Barbara , Dickstein Ruth , Desmond Nancy L. , Levy William B. 
Published: January 2005

AbstractThis report further characterizes associative long‐term synaptic modification of the ipsilateral and contralateral synapses formed by the bilateral entorhinal cortical (EC) projection to the dentate gyrus (DG). The experimental model is the anesthetized hooded rat. The quatntitative results qualify this system as a model for studying the rules of associative synaptic modification formulated in terms of individual synapses. Bilateral DG microelectrodes recorded both ipsilateral and contralateral EC‐DG responses before and after brief, high‐frequency EC conditioning stimulatin. The weak contralateral pathway receivewd high‐frequency coditioning before, during, or after similar conditioning of the strong, converging ipsilateral pathway. Statistical analyses revealed two types of significant, dissociated synaptic modifications, which depend on the relationship of the ipsilateral and contralateral afferents. First, contralateral EC‐DG responses potentiated, depressed, or showed no change when the collateral ipsilateral responses concurrently either potentiated or remained unchanged. Correlation and contingency table analysis indicated that changes in the contralateral synaptic responses are not well predicted by changes at either neighboring synapses of the converging ipsilateral pathway or at synapses of the collateral ipsilateral pathway. The contingencies of associated pre‐ and postsynaptic activation determined by the conditioning paradigm, however accurately predicted the altered synaptic responses of both ipsilateral and contralateral rately predicted the altered synaptic responses of both ipsilateral and contralateral EC‐DG pathways. The results imply that associative synaptic modification in the EC‐DG system is specific to individual synapses and requires both appropriate presynaptic and postsynaptic activation. Because this system provides suitable controls for nonspecific dissociable, the EC‐DG system can be used to study further those rules of activity‐dependent associative modification that are formulated in terms of individual synapses. The discussion briefly considers published rules modification, pointing out several rules that are not consistent with the ecperimental observations and one that agrees with the present results.
GABA and glutamate receptor development of cultured neurons from rat hippocampus, septal region, and neocortex
Authors: Köller Hubertus , Siebler Mario , Schmalenbach Corinne , Müller Hans‐Werner 
Published: January 2005

AbstractThe early development of functionally active GABA and glutamate receptors on neurons from hippocampus, septal region, and neocortex of embrryonic rats were studied using primary dissociated serum‐free cell cultures. The responses to GABA and glutamate, applied to individual neurons by pressure ejection, were tested at different development stages, starting at 1 day in vitro (DIV) until 3 weeks. In all three types of neuronal cultures, the GABAA‐receptor developed prior to the glutamate receptros, and after 9 DIV most of the neurons were sensitive to both GABA and glutamate. N‐methyl‐D‐aspartate (NMDA) and non‐NMDA receptor subtypes of the glutamate receptors could be distinguished in hippocampal cultures. The development of GABA and glutamate receptors on septal region neurons appeared to be delyed as compared to hippocampal neurons. In neucortical cultures the majority of nueorns was sensitive to GABA just after plating, whereas the sensitivity to glutamate was retarded. The differences in GABA and glutamate receptor development among these three neuronal cultures provide evidence that the apearance of tranmitter receptors on cultured neurons is predominantly determined by intrinsic mechanisms rather than by environmental coditions. The proportion of spontaneously active networks in these cultures increased with a time course very similar to the rise in glutamate‐sensitive neurons suggesting that functional active glutamate receptors may be involved in the generation of spontaneous activity.
Subtypes of excitatory amino acid receptors involved in the stimulation of [3H]dopamine release from cell cultures of rat ventral mesencephalon
Authors: Mount Howard , Quirion Rémi , Kohn‐Alexander Judity , Boksa Patricia 
Published: January 2005

AbstractN‐methyl‐D‐aspartic acid (NMDA), quisqualic acid (QUIS), and kainic acid (KAIN), respective agonists for three excitatory amino acid (EAA) receptor subtyes, stimulated [3H]dopamine ([3H]DA) release from dissociated cell cultures of fetal rat ventral mesencephalon. Release evoked by all three agonist was Ca2+‐dependent and inhibited by broad‐spectrum antagonists (D, L‐cis‐2, 3‐piperidine dicarboxylic acid [PDA] and kynurenic acid [KYN]). However, both of these antagonists were more potent against KAIN than against QUIS and only KAIN‐evoked release was blocked by γ‐D‐glutamylaminomethyl sulfonic acid (GAMS, IC50 700 m̈M). NMDA‐stimulated [3H]DA release was selectively inhibited by competitive (3‐[2‐carboxypiperazine‐4‐yl]propyl‐1‐phosphonic acid [CPP] and D, L‐2‐amino‐5‐phosphonvaleric acid [APV]) and non‐competitive (phencyclidine and MK‐801) NMDA receptor antagonists. In 1.2 mM Mg2+, NMDA‐stimulated [3H]DA release was NA+‐dependent and inhibited by tetrodotoxin (TTX, 2 m̈M) or by the local anaesthetic, lidocaine (200 m̈M). However, in 0 Mg2+, NDMA‐evoked release was not inhibited by TTX or lidocaine. Thus, TTX‐sensitivity of the NMDA response in 1.2 mM Mg2+ apparently occurs because Na+‐action potentials are required to alleviate a Mg2+ blockade. Neither QUIS‐nor KAIN‐evoked release was affected by Mg2+ or TTX. When extracellular NaCI was replaced by sucrose or Na2SO4, the QUIS response was increased. KAIN‐evoked release was unaffected by the sucrose substitution and was attenuated in the Na2SO4‐containing buffer.It is concluded that NMDA and QUIS/KAIN release [3H]DA via separate receptor subtypes.
Neurotensin binding sites in porcine jejunum: Biochemical Characterization and intramural Localization
Authors: Seybold Virginia S. , Treder Bradley G. , Aaonsen Linda M. , Parsons Ann , Brown David R. 
Published: January 2005

AbstractNeurotensin is present in high concentrations in the mammalian gut, especially in enteroendocrine cells of the mucose. Exogenous neurotensin has been shown to alter ion transport by the mucosa and contractile activity of intestinal smooth muscle. The purpose of this study was to determine the distribution of neurotensin binding sites withing the intestinal wall. Initially, biochemical characteristics of [125I]neurotensin binding sites were determined within two preparations of the distal porcine jejunum: (1) the mucosa and submucosa, and (2) the circular and longitudinal muscle with their intramural plexuses. Ligand binding data for the preparation including the mucosa and submucosa indicated that [125I]neurotensin bound specifically to two sites having apparent equilibrium dissociation constants of approximately 0.46 and 0.37nM. A binding site with a dissociation constant of approximately 0.38 nM was confirmed for the preparation of muscle and associated intramural plexuses. Xenopsin and neurotensin<sb6–13 were approximately 40 times less potent in the preparation of mucosa and submucosa.Receptor autoradiography was used to determine the distribution of [125I]neurotensin binding sites within the wall of the jejunum. Autoradiograms of [125I]neurotensin bound to cross sections of the proximal and distal jejunum showed that the highest densities of silver grains were associated with the internal submucosal gangilia, external submucosal plexus and myenteric ganglia. A moderate density of silver grains was associated with the circular muscle.The localization of neurotensin binding sites to submucosal ganglia is consistent with observations that neurotensin effects on active anion secretion by the mucosa are blocked by tetrodotoxin. Immunohistochemical localization of neurotensin in the porcine jejunum demonstrated a limited population of neurotensin immunoreactive cells within the mucosal epithelium. It is possible that neurotensin released from these cells in the mucosa as well as neurotensin‐related peptides released from enteric neurons may be the endogenous ligands for the binding sites visualized in this study.
Autoradiographic localization of delta opioid receptors within the mesocorticolimbic dopamine system using radioiodinated [2‐d‐penicillamine, 5‐d‐penicillamine]enkephalin (125I‐DPDPE)
Authors: Dilts Roger P. , Kalivas Peter W. 
Published: January 2005

AbstractThe enkephalin analog [2‐D‐Penicillamine, 5‐D‐Penicillamine]enkephalin was radioiodinated 125I‐DPDPE and shown to retain a pharmacological selectivity characteristic the delta opioid receptor in in vitro binding studies. The distributions of 125I‐DPDPE binding, using in vitro autoradiographic techniques, were similar to those previously reported for the delta opioid receptor. The nucleus accumbens, striatum, and medial prefrontal cortex contain dense gradients of 125I‐DPDPE binding within particular regions of the mesocorticolimbic dopamine system. Unilateral lesions of dopamine perikarya (A9 and A10) within the ventral tegmental area nd substantia nigra produced by mesencephalic injection of 6‐hydroxydopamine resulted in significant (20–30%) increase in 125I‐DPDPE binding contralateral to the lesion within the striatum and nucleus accumbens. Lesions of the perikarya (dopaminergic and nondopaminergic) of the ventral tegmental area, induced by aquinolinic and injections, caused increases of less magnitude within these same nuclei. No significant alteratons in 125I‐DPDPE binding were observed within the mesencephalon as a result of either treatment. The specificity of the lesions was confiremed by immunocytochemistry for tyrosine for tyrosine hydroxylase. These results suggest that the enkephalins and opioid agonists through delta opioid receptors do not dircetly modulate dopaminergic afferents but do regulate postsnaptic targets of the mesocorticolimbic dopamine system.