bluuebunny/crossref_metadata_2025_split huggingface dataset:
The GABAA receptor channel mediated chloride ion translocation through the plasma membrane: New insights from 36Cl− ion flux measurements
Authors: Kardos J. 
Published: December 2004

AbstractGABAA receptors in plasma membranes of neurons are integral oligomers which form chloride channels. The binding of GABA molecules at recognition sites for channel opening triggers a transient increase in transmembrane chloride ion flux. The multiplicity and drug specificity of GABAA receptor, kinetics of channel opening, and desensitization of GABAA receptor and its short‐ and long‐term regulation have been investigated by the use of tracer amounts of the radioactive chloride isotope, 36Cl− ion. Results and new insights from 36Cl− ion flux measurements have been reviewed. © 1993 Wiley‐Liss, Inc.
LSD has high efficacy relative to serotonin in enhancing the cationic current Ih: Intracellular studies in rat facial motoneurons
Authors: Garratt Jennifer C. , Alreja Meenakshi , Aghajanian George K. 
Published: December 2004

AbstractThe effects of LSD (d‐lysergic acid diethylamide) on rat facial motoneurons were compared to those of 5‐hydroxytryptamine (5‐HT) in brain slices by means of current clamp and single‐electrode voltage‐clamp recordings. As previously reported, 5‐HT, in part by decreasing a resting potassium conductance, produced a reversible depolarization (∼5 mV), an increase in input resistance, and an enhancement in electrical excitability. LSD also produced an increase in electrical excitability, although with a much slower onset and longer duration. However, in contrast to 5‐HT, LSD produced only a slight depolarization (1‐2 mV). Moreover, in the presence of LSD the depolarizing effect of 5‐HT was markedly attenuated. The 5‐HT2/5‐HT1c agonist 1‐(2,5‐dimethoxy‐4‐io‐dophenyl)‐2‐aminopropane (DOI) produced effects intermediate between LSD and 5‐HT. The LSD‐induced increase in electrical excitability was completely reversed by spiperone, a 5‐HT2/5‐HT1A antagonist, and by ritanserin, a 5‐HT2/5‐HT1c antagonist; the effects of 5‐HT were also reduced by these 2 antagonists, but complete blockade did not occur at the concentrations and durations tested. Surprisingly, LSD was found to enhance the hyperpolarization‐activated nonspecific cation current Ih to a greater extent than did 5‐HT; this enhancement was blocked by both spiperone and ritanserin. These results indicate that, despite having low efficacy relative to 5‐HT in decreasing resting potassium conductance, LSD has high efficacy in enhancing the Ih current in rat facial motoneurons; possible mechanisms for this difference are discussed. © 1993 Wiley‐Liss, Inc.
Physiological and morphological properties of accumbens core and shell neurons recorded in vitro
Authors: O'Donnell Patricio , Grace Anthony A. 
Published: December 2004

AbstractThe morphology and electrophysiological properties of neurons in the nucleus accumbens were studied using intracellular recording techniques in rat brain slices maintained in vitro. Neurons were subdivided according to their location in the shell or core region of the nucleus accumbens. Most of the cells in both regions had small to medium‐sized (15.8 ± 2.8 μM) somata with densely spinous dendrites, somewhat similar to the striatal medium spiny neuron. However, minor morphological differences between neurons from accumbens core and shell regions were found, such as fewer primary dendrites in shell neurons than in the core (3.8 ± 0.8 vs. 4.4 ± 1.0) and the spatial organization of their dendritic trees. In general, the passive membrane properties of neurons in each region were similar. However, shell neurons appeared to be less excitable in nature, as suggested by (1) a faster time constant, (2) the absence of TTX‐insensitive events resembling low‐threshold spikes, and (3) the lower probability of evoking spikes in shell neurons by stimulation of amygdaloid or cortical afferents in comparison to the responses of coreneurons to cortical afferent stimulation. In most nucleus accumbens neurons the action potentials evoked by membrane depolarization were preceded by a slow Ca2+‐dependent depolarization and showed firing‐frequency adaptation. Following TTX administration, all‐or‐none spike‐like events resembling high‐threshold calcium spikes were observed in both regions. In summary, except for minor differences, most of the properties of core and shell neurons are similar, supporting their characterization as subdivisions of a single structure. Therefore, differences in the functional properties of these neuronal populations are likely to be due to their distinct connectivity patterns. © 1993 Wiley‐Liss, Inc.
Behavioral indices of moderate nigro‐striatal 6‐hydroxydopamine lesion: A preclinical Parkinson's model
Authors: Fornaguera J. , Schwarting R. K. W. , Boix F. , Huston J. P. 
Published: December 2004

AbstractAsymmetries in turning and scanning were investigated in rats with different degrees of neostriatal dopamine depletion after unilateral injections of 6‐hydroxydopamine into the substantia nigra. Animals with severe lesions, i. e., residual dopamine levels of <20%, spontaneously turned ipsiversive and showed more scanning behavior with the side ipsilateral to the lesion. These asymmetries were reversed by the dopamine receptor agonist apomorphine. Animals with less severe dopamine depletion, i. e., residual dopamine levels of 20–65%, did not show an asymmetry in spontaneous turning, but an ipsilateral asymmetry in scanning was still observed, indicating a greater sensitivity of this measure for moderate striatal dopamine depletions. Furthermore, in animals with residual dopamine levels of 45–65%, the dopamine receptor agonist apomorphine did not lead to a behavioral reversal as with severe lesions, but induced ipsilateral scanning and ipsiversive turning. These ipsiversive asymmetries are discussed in relation to asymmetries in self‐regulatory mechanisms of the nigro‐striatal dopamine system, such as dopamine autoreceptors controlling the release of this transmitter. Dopamine receptor‐stimulated behavioral asymmetry in animals with moderate depletions of dopamine is suggested as a preclinical model to study mechanisms affected in the early state of Parkinson's disease. © 1993 Wiley‐Liss, Inc.
Long‐lasting potentiation of synaptic transmission in the schaffer collateral‐commissural pathway of the guinea pig hippocampus by activation of postsynaptic N‐methyl‐D‐aspartate receptor
Authors: Kamiya Haruyuki , Sawada Satsuki , Yamamoto Chosaburo 
Published: December 2004

AbstractThe effects of short‐period (2 min) perfusion of conditioning solution, which contains N‐methyl‐D‐aspartate (NMDA), glycine, and spermine, on the synaptic transmission in the Schaffer collateral‐commissural pathway were examined in hippocampal slices with the intracellular recording technique. Long‐lasting potentiation of excitatory postsynaptic potentials (EPSPs) was induced (as long as the records lasted, up to 3 h in the longest observation) after membrane potentials of postsynaptic neurons were depolarized by current injection during perfusion of the conditioning solution. D‐2‐amino‐5‐phoshonovaleric acid (D‐AP5), a specific antagonist of NMDA receptors, block the induction of the long‐lasting potentiation by perfusion of NMDA containing solution. This potentiation was accompanied by a decrease in the relative magnitude of EPSP amplitude fluctuation (coefficient of varation, CV). The reciprocals of squared CVs (= mean2/variance) were almost proportional to the magnitude of the potentiation, and the ratios of 1/CV2 and the magnitudes of potentiation were not different from those of long‐term potentiation (LTP) induced by tetanic stimulation. These findings suggest that long‐lasting potentiation is induced solely by activation of postsynaptic NMDA receptors, and transmitter release from presynaptic terminals may be modified by the activation of postsynaptic receptors. © 1993 Wiley‐Liss, Inc.
In vivo assessment of basal and drug‐induced dopamine release in cortical and subcortical regions of the anesthetized primate
Authors: Moghaddam Bita , Berridge Craig W. , Goldman‐Rakic Patricia S. , Bunney Benjamin S. , Roth Robert H. 
Published: December 2004

AbstractThere is an acute interest in studying the functional characteristics of dopamine systems in the cortex of primates. In particular, the prefrontal cortical dopamine projections have received a great deal of attention. This system is essential for proper functioning of the prefrontal cortex, and dysfunction within the system may be involved in some psychiatric and neurological illnesses. In vivo assessments of cortical dopamine in the primate have been scarce. This has been due, in part, to technical difficulties associated with these studies and with quantifying the relatively low levels of dopamine found in cortical regions. In the present study, intracerebral microdialysis was utilized to assess the extracellular concentration of dopamine in cortical and subcortical areas of the pentobarbital‐anesthetized rhesus monkey. Basal extracellular dopamine levels were consistently detected in the medial prefrontal cortex, premotor cortex, and caudate‐putamen. The basal extracellular concentration of dopamine in the dorsolateral prefrontal cortex was reliably detected in 1 of 4 animals. Intravenous administration of amphetamine (1 mg/kg) enhanced extracellular dopamine levels in the caudate‐putamen area by more than 20‐fold. In cortical areas, amphetamine's effect was less profound: An increase of 400–500 percent over basal extracellular dopamine levels was observed in each region. These studies demonstrate the feasibility of microdialysis for detecting extracellular fluxes of dopamine in the cortex of nonhuman primates. They further provide direct evidence that the dopamine released within the prefrontal cortex and the premotor cortex of nonhuman primates responds to pharmacological manipulation. © 1993 Wiley‐Liss, Inc.
SPECT imaging of dopamine and serotonin transporters with [123I]β‐CIT: Pharmacological characterization of brain uptake in nonhuman primates
Authors: Laruelle Marc , Baldwin Ronald M. , Malison Robert T. , Zea‐Ponce Yolanda , Zoghbi Sami S. , Al‐Tikeriti Mohammed S. , Sybirska Elzbieta H. , Zimmermann Ralph C. , Wisniewski Gary , Neumeyer John L. , Milius Richard A. , Wang Shaoyin , Smith Eileen O. , Roth Robert H. , Charney Dennis S. , Hoffer Paul B. , Innis Robert B. 
Published: December 2004

AbstractSingle photon emission computed tomography (SPECT) studies of regional kinetic uptake and pharmacological specificity of [123I] methyl 3β‐ (4‐iodophenyl) tropane‐2β‐carboxylate ([123I]β‐CIT) were performed in nonhuman primates (n = 41). In control experiments, activity was concentrated in striatum and in hypothalamic/midbrain regions. Striatal uptake increased for 140–180 min and displayed stable levels thereafter. Striatal to cerebellar activity rations were 7.3 ± 0.9 (mean ± SEM) at 300 min. About 75% of striatal uptake was displaceable by injection of nonradioactive β‐CIT. Hypothalamic/midbrain activity reached maximal levels at approximately 45 min. A slow washout phase followed this peak activity. Activities in frontal, occipital, and cerebellar regions were characterized by an early peak (20–30 min), followed by rapid washout. Displacement studies demonstrated that striatal uptake was associated with dopamine (DA) transporters, as it was displaced by GBR 12909, a selective DA uptake inhibitor, but not by citalopram, a selective serotonin (5‐HT) uptake inhibitor. The inverse was true in the hypothalamic/midbrain area, suggesting that the uptake in this area was associated primarily with 5‐HT transporters. Maprotiline, a selective norepinephrine uptake inhibitor, did not affect [123I]β‐CIT uptake. In vivo site occupancy ED50 values of cocaine, 2β‐carbomethoxy‐3β‐(4‐fluorophenyl) tropane (CFT), and β‐CIT were measured in the striatum with a stepwise displacement paradigm. In vivo ED50 values correlated strongly with in vitro IC50 values for binding to DA transporters. Infusion of high dose of L‐DOPA (250 μMol/kg) failed to displace striatal [123I]β‐CIT binding, suggesting that the binding would not be affected by L‐DOPA administration in Parkinsonian patients. However, studies performed with injection of d‐amphetamine indirectly suggested that high synaptic levels of DA may compete with [123I]β‐CIT binding, These studies suggest that [123I]β‐CIT will be a useful SPECT tracer of DA and 5‐HT transporters in living human brain. © 1993 Wiley‐Liss, Inc.
Molecular alterations in the neostriatum of human cocaine addicts
Authors: Hurd Yasmin L. , Herkenham Miles 
Published: December 2004

AbstractMolecular changes in the neostriatum of human subjects who died with a history of cocaine abuse were revealed in discrete cell populations by means of the techniques of in situ hybridization histochemistry and in vitro receptor binding and autoradiography. Cocaine subjects had a history of repeated cocaine use and had cocaine and/or cocaine metabolites on board at the time of death. These subjects were compared to control subjects that had both a negative history and toxicology of cocaine use. Selective alterations in mRNA levels of striatal neuropeptides were detected in cocaine subjects compared to control subjects, especially for the opioid peptides. Marked reductions in the levels of enkephalin mRNA and μ opiate receptor binding were found in the caudate and putamen, concomitant with elevations in levels of dynorphin mRNA and κ opiate receptor binding in the putamen and caudate, respectively. Dopamine uptake site binding was reduced in the caudate and putamen of cocaine subjects. The greater magnitude of changes in the dorsolateral striatum (caudate and putamen) as opposed to the ventromedial striatum (nucleus accumbens) suggests that cocaine abuse preferentially alters the biosynthetic activity of striatal systems associated with sensorimotor functioning. Additionally, an imbalance in the activity of the two major striatal output pathways in cocaine users is implicated because peptide mRNA levels were reduced in enkephalinergic striatopallidal neurons and increased in dynorphinergic striatonigral neurons. Another imbalance, that of reductions of transmitter mRNA and receptor expression associated with euphoria (enkephalin and μ opiate receptors), together with elevations in mRNAs of transmitter systems associated with dysphoria (dynorphin and κ opiate receptors), suggests a model of dysphoria and craving in the human cocaine addict brain. © 1993 Wiley‐Liss, Inc.
Extracellular glutamate levels increase with age in the lateral striatum: Potential involvement of presynaptic D‐2 receptors
Authors: Donzanti Bruce A. , Hite Juliana F. , Yamamoto Bryan K. 
Published: December 2004

AbstractIn the lateral striatum of aged rats, dopamine D‐2 receptor density is reduced and glutamate tissue content is elevated. D‐2 receptor agonists have been shown to inhibit stimulated glutamate release. In the present study, microdialysis was used to investigate a potential role for D‐2 receptors in the modulation of striatal glutamate efflux from 4‐, 12‐, 18‐, and 24–26‐month‐old Fischer 344 rats. Extracellular basal glutamate concentrations significantly increased as a function of age in the lateral, but not medial, striatum. Neither the D‐2 agonist, LY 163502, nor the D‐2 antagonist, sulpiride, influenced basal glutamate efflux, suggesting that the dopaminergic system is not involved in the observed age‐related increase in extracellular basal glutamate levels. In contrast to basal efflux, potassium‐evoked glutamate release was not altered with age. However, LY 163502 significantly inhibited stimulated glutamate release in 4‐month‐old rats. This inhibitory action was not observed at any other age. Sulpiride alone did not alter stimulated glutamate release, but it did block the inhibitory effect of LY 163502 in the 4‐month‐old rats. These results provide in vivo evidence for an age‐related functional loss in the modulation of striatal glutamate release by dopamine D‐2 receptors in addition to increased basal glutamate efflux, which is not related to D‐2 receptor modulation. Such mechanisms could be important in the pathophysiology of striatal cell death during aging and age‐related neurodegenerative diseases. © 1993 Wiley‐Liss, Inc.
Identification of a GBR12935 homolog, LR1111, which is over 4,000‐fold selective for the dopamine transporter, relative to serotonin and norepinephrine transporters
Authors: Rothman Richard B. , Lewis Bruce , Dersch Chris , Xu Heng , Radesca Lillian , De Costa Brian R. , Rice Kenner C. , Kilburn Robert B. , Akunne Hyacinth C. , Pert Agu 
Published: December 2004

AbstractThe di‐substituted piperazines, GBR12909 (1‐[2‐[bis(4‐fluorophenyl)‐methoxy]ethyl]‐4‐[3‐phenylpropyl]piperazine) and GBR12935 (1‐[2‐(diphenyl‐methoxy)‐ethyl]‐4‐(3‐phenylpropyl)piperazine), are potent and selective (20‐to 100‐fold) inhibitors of [3H]dopamine reuptake, relative to [3H]5‐HT and [3H]norepinephrine uptake. The GBR12935 analog, 1‐(2‐(diphenylmethoxy)ethyl)‐4‐(3‐phenylpropyl)homopiperazine (LR1111), was synthesized as part of a systematic structure‐activity study of analogs of GBR12935 and GBR12909. LR1111 differs from GBR12935 by the addition of a methylene group into the piperazine ring to yield a compound with a seven‐member homopiperazine ring. The IC50 values for LR1111 at the dopamine, norepinephrine, and serotonin transporters were 7.2 nM, 34, 072 nM, and greater than 20,000 nM, respectively, whereas the IC50 values of GBR12935 were 3.7 nM, 289 nM, and 1261 nM for these same transporters. This demonstrates that the addition of a single methylene group in the piperazine ring results in a compound with similar affinity but significantly higher selectivity for the dopamine transporter. LR1111 increased motoric activity in rats after intravenous administration. These indicate that LR1111 is a potent and highly selective inhibitor of the dopamine transporter. Published 1993 Wiley‐Liss, Inc.
Differential pharmacological profile of striatal and cerebellar dopamine receptors labeled by [3H]quinpirole: Identification of a discrete population of putative D3 receptors
Authors: Levant Beth , De Souza Errol B. 
Published: December 2004

AbstractWe have previously identified [3H]quinpirole‐labeled dopamine receptors in the molecular layer of cerebellar lobule 10 which have a D2‐like pharmacological profile, are guanine nucleotide‐insensitive, and are juxtaposed to putative D3 receptor mRNA. This study compares the pharmacological profiles of [3H]quinpirole‐labeled dopamine receptors in striatum and cerebellar lobule 10 using quantitative autoradiography. Dopaminergic compounds inhibited the specific binding of [3H]quinpirole in the caudate/putamen with the following rank order of potencies: spiperone > haloperidol ≥ (+)butaclamol ≥ quinpirole ≥ 7‐OH‐DPAT ≥ bromocriptine > clozapine > (‐)sulpiride. In cerebellar lobule 10, a somewhat different rank order of potencies was observed: 7‐OH‐DPAT > quinpirole ≥ bromocriptine > spiperone > (+)butaclamol > haloperidol > clozapine > (‐)sulpiride. Quinpirole possessed equal affinity for [3H]quinpirole‐labeled receptors in the caudate/putamen and cerebellum. 7‐OH‐DPAT exhibited 5‐fold greater affinity for cerebellar receptors than those in the caudate/putamen. Spiperone, haloperidol, (+)butaclamol, and clozapine were more potent in competing for [3H]quinpirole binding at striatal dopamine receptors than cerebellar receptors by 83‐, 59‐, 11‐, and 6‐fold, respectively. The relative potencies of these compounds at striatal and cerebellar dopamine receptors are generally similar to the differential affinities reported at D2 and D3 dopamine receptors expressed in CHO cells, respectively. These data provide additional evidence that the dopamine receptors observed in cerebellar lobule 10 represent a discrete population of putative D3 receptors. © Wiley‐Liss, Inc.
Expression of adenosine A1 receptors in cultured neurons from fetal rat brain
Authors: Nicolas Frédéric , Daval Jean‐Luc 
Published: December 2004

AbstractThe expression of adenosine A1 receptors was investigated using [3H]2‐chloro‐N6 ‐cyclopentyladenosine (CCPA) in 8‐day‐old cultured neurons from fetal rat forebrain grown in serum‐free medium. [3H]CCPA bound specifically and with high affinity (Kd = 2.9 nM) to a homogeneous population of sites. Displacement of CCPA binding by various adenosine derivatives indicated that A1 receptors were selectively labeled. The presence of Gpp(NH)p, a GTP analogue, reduced significantly the binding affinity (Kd = 12.2 nM), suggesting that A1 receptors detected in intact cultured cells are linked to associated G proteins. © 1993 Wiley‐Liss, Inc.
Depolarization inactivation of dopamine neurons: Terminal release characteristics
Authors: Moghaddam Bita , Bunney Benjamin S. 
Published: December 2004

AbstractThe functional consequences of chronic treatment with haloperidol (0.5 mg/kg s. c. for 21–23 days) on striatal extracellular levels of dopamine and excitatory amino acids, aspartate and glutamate, were examined using microdialysis techniques. Our studies indicate that, in both awake and anesthetized animals, chronic haloperidol treatment does not appear to change basal outflow of dopamine and its response to an exogenous antagonist (i. e., a challenge dose of haloperidol). Furthermore, in chronic haloperidol and vehicle‐treated animals, extracellular dopamine levels were decreased below our limit of detection following perfusion of tetrodotoxin through the probe, or into the medial forebrain bundle, suggesting that in both groups of animals extracellular dopamine levels are neuronally derived and seemed to depend equally on impulse flow. However, some differences were observed between the vehicle and haloperidol‐treated animals: the excitatory action of 30 mM K+ on extracellular dopamine levels was decreased, and extracellular levels of glutamate were significantly increased, in animals treated chronically with haloperidol. The alterations in extracellular glutamate levels suggests that events at the terminal may be involved in maintaining the “normal” extracellular dopamine levels. Furthermore, the decrease in response to stimulation by K+ suggests that chronic haloperidol treatment may decrease the responsivity of the striatal dopamine system to stimuli. © 1993 Wiley‐Liss, Inc.
Paroxysmal long‐lasting depolarizations in cultured hippocampal neurons are generated by activation of NMDA and non‐NMDA receptors
Authors: Köller Hubertaus , Siebler Mario , Müller Hans Werner 
Published: December 2004

AbstractIn primary cultures of hippocampal neurons from the embryonic rat, spontaneous depolarizations lasting up to 6 sec adn resembling paroxysmal depolarization shifts (PDAs) appeared after 11 day7s in vitro. These depolarizations are presumably generated by sy6naptic events, because: (1) both their appearance and duration are independent of membrane potential, (2) the amplitudes of the underlying currents depend monotonically on membrane potential, and (1) they are reversed at the reversal potential of the excitatory postsynaptic potentials (EPSPs). In addition, PDAs disappeared reversiblyy when sodium‐dependent action potentials were blocked by tetrodotoxin (10μM) and when synaptic transmission was reduced by elevated Mg2+ (5mM). Further, the fact that these depolarizations can apppear simultaneously in two neurons in paired recordings also points to a synaptic origin. Inhibition of glutaminergic synaptic transmission by kynurenic acid (50μM) and the NMDA‐antagonist D‐2‐amino‐5‐phosphonovaleric acid (APV; 50μM) led to a marked shortening of the depolarizations. This blocking effect of kynurenic acid and APV and comparison with the currents elicited by locally applied glutamate or NMDA provide evidence for an activation of both types of glutamate receptors to induce PDSs. The role of alteration of glutaminergic synaptic transmission in the induction and maintenance of these depolarizations is discussed in the context of results from the literature on the appearrance of PDSs in cultures grown under chronic blockade of glutamate receptors. © 1993 Wiley‐Liss, Inc.